CN102311402B - Preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone - Google Patents
Preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone Download PDFInfo
- Publication number
- CN102311402B CN102311402B CN2011102007143A CN201110200714A CN102311402B CN 102311402 B CN102311402 B CN 102311402B CN 2011102007143 A CN2011102007143 A CN 2011102007143A CN 201110200714 A CN201110200714 A CN 201110200714A CN 102311402 B CN102311402 B CN 102311402B
- Authority
- CN
- China
- Prior art keywords
- substituted
- ketone
- ester
- phenyl
- oxazolidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone. Substituted aniline which is treated as an initial substance is condensed with glycidol to synthesize an intermediate (R)-(+)-3-substituted phenylamino-1,2-propylene glycol, and a two-step reaction is carried out to prepare 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone. The obtained product 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone is an important intermediate for commercial production of oxazolidinone antiseptics. The preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone with the two-step reaction which has the characteristics of less step, simple operation, easily obtained and cheap raw material, mild reaction condition and the like, and has the advantages of improvement of the production efficiency, reduction of the production energy consumption, improvement of the production safety coefficient, reduction of the production cost, and reduction of the environmental pollution is a synthetic method with environmental protection and low carbon.
Description
Technical field
The present invention relates to a kind of preparation method of pharmaceutical intermediate, be specifically related to a kind of preparation method of key intermediate 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone of oxazolidinones antiseptic-germicide processed.
Background technology
Oxazolidine ketone antiseptic-germicide is the antibacterial agent that a class mechanism of action is different from other various antiseptic-germicides.3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone is that the synthetic necessary key intermediate of this class medicine is (referring to Steven JB, et a1.J Med Chem, 1996,39 (3): 673-679; Meng Qingguo, Wang Qi, Liu Jun, Acta Pharmaceutica Sinica, 2003,38(10): 754~759; Barbachyn, MR etc., WO9507271; Barbachyn, MR etc., ZL94193313.x; The pendant Germania, BA etc., ZL97193658.7; The pendant Germania, BA etc., ZL01133003.1; Xu Guangyu etc., ZL200410017127.0; Barbachyn, MR etc., ZL200510048548.4).
In the prior art, the preparation method of 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone, great majority adopt substituted aniline to react with chloroformic acid benzyl ester earlier, substituted-phenyl-the benzyl carbamate that generates reacts (Steven JB with the Racemic glycidol butyric ester again, et a1.J Med Chem, 1996,39 (3): 673-679; ZL94193313.x, WO9507271; Acta Pharmaceutica Sinica, 2003,38(10): 754~759), reaction formula is as follows:
The reaction conditions of this method is relatively harsher, needs to use butyllithium reagent and very low temperature (78 ℃); When suitability for industrialized production, the Pei Erman of Pharmacia ﹠ Upjohn S.P.A etc. improves reaction, temperature of reaction can be elevated to-10 ℃~-28 ℃ (ZL01133003.1, ZL03159474.3, ZL97193658.7), and use S-(+)-3-chloro-1,2-propylene glycol or Racemic glycidol replace the Racemic glycidol butyric ester, and production technique is more simple.Reaction formula is as follows:
The Xu Guangyu of Shanghai Pharmaceutical Inst., Chinese Academy of Sciences etc. react with (the S)-Glycerose of substituted aniline and acetone protection, the imines that generates is with 10% palladium-hydrocarbonize, use hydrogenchloride ethanol deprotection base then, obtain 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone (ZL200410017127.0) with the triphosgene cyclization at last; Though this method does not re-use the such reagent of butyllithium, step is more, and is cumbersome; Reaction formula is as follows:
Product III wherein is not disclosed in this article.
The Huang Qiang of Zhengzhou University etc. use substituted aniline and phosgene reaction to generate the substituted-phenyl isocyanide ester, react with Glycidyl butyrate then, last sodium bicarbonate aqueous solution hydrolysis obtains 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone (ZL200510048548.4), and this method need be used lithiumbromide and tributyl phosphorus oxide.Reaction formula is as follows:
There are various deficiencies in aforesaid method, some method severe reaction conditions, some method steps complexity; And its common shortcoming is to use the carbon atom utilization ratio of reagent lower, for example, chloroformic acid benzyl ester the earliest-Racemic glycidol butyric ester route, the carbon atom utilization ratio of reagent chloroformic acid benzyl ester has only 1/8, and total atom utilization also has only 1/9; The carbon atom utilization ratio of Racemic glycidol butyric ester is 3/7, and total atom utilization is 5/11.Chloroformic acid benzyl ester after the improvement-3-propylene glycol of chlorine route does not change the atom utilization of chloroformic acid benzyl ester, is that atom utilization is very high and use 3-propylene glycol of chlorine great advantage, and total atom utilization brings up to 11/13; The glycidaldehyde route of domestic scholars improvement, the carbon atom rate of glycidaldehyde has only 1/2; And the isocyanide ester route has used the not high Racemic glycidol butyric ester of atom utilization.The carbon atom utilization ratio is not high, means to have produced organic by-products in the reaction process, and therefore, also just meaning has wasted resource, and has caused the pollution of environment, and not only production cost is higher, does not meet low-carbon (LC), the synthetic development trend of environment-friendly and green yet.
Summary of the invention
Goal of the invention of the present invention provides the preparation method of a kind of 3-substituted-phenyl-5-hydroxyl first base oxazolidine-2-ketone, when simplifying preparation technology, making the reaction conditions gentleness, improves the utilization ratio of carbon atom, to reduce the pollution to environment.
To achieve the above object of the invention, the technical solution used in the present invention is: the preparation method of a kind of 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone, and the structural formula of described 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone is:
In the formula, R
1Be halogen, preferred fluorine; R
2Be nitrogen heterocyclic ring or replacement aromatic ring;
Z in the formula
1Be O, S or NR
4R
4Be amine protecting group, as benzyl, substituted benzyl, formic acid ester group, carboxylic acyl radical, alkylsulfonyl; Z
1Preferred O or S;
R
3Alkyl for C1-C4;
R wherein
6Alkyl for C1-C6; R
7Be amine protecting group, as benzyl, substituted benzyl, formic acid ester group, carboxylic acyl radical, alkylsulfonyl; R
8Be amine protecting group, as benzyl, substituted benzyl, formic acid ester group, carboxylic acyl radical, alkylsulfonyl;
Substituted aniline with formula II is raw material,
R in the formula
1, R
2Definition the same,
With Racemic glycidol by synthetic intermediate (R)-(+)-3-substituted benzene amino-1 that obtains of condensation reaction, 2-propylene glycol, the structural formula of described Racemic glycidol be,
Described (R)-(+)-3-substituted benzene amino-1, the structural formula of 2-propylene glycol is,
R in the formula
1, R
2Definition the same,
With the reaction of compound III and carbonyl derivative, namely obtain target compound again, the structural formula of described carbonyl derivative is,
Wherein, X
2, X
3Be leavings group, be selected from C1~C4 alkoxyl group, the benzyloxy of halogen, halogen replacement
,Phenoxy group or imidazolyl that phenoxy group, ortho position or a position or contraposition halogen or nitro replace, X
2, X
3Can be identical, also can be different.
Technique scheme can be expressed as:
In the technique scheme, in described substituted aniline and the Racemic glycidol reaction, substituted aniline is 0.8~5:1 with the ratio of the amount of substance of Racemic glycidol; Used organic solvent is selected from alcohol, ether or methane amide; Temperature of reaction is 20~100 ℃.
Optimized technical scheme, substituted aniline is that the used organic solvent of 0.8~1.5:1 is selected from methyl alcohol, ethanol, Virahol, ether, tetrahydrofuran (THF), diisopropyl ether or DMF with the ratio of the amount of substance of Racemic glycidol; Temperature of reaction is 60~80 ℃.
In the technique scheme, (R)-(+)-3-substituted benzene amino-1, the 2-propylene glycol is 1:1~2 with the ratio of the amount of substance of carbonyl derivative; Used organic solvent is selected from alcohol, ether or methane amide; Temperature of reaction is-20~20 ℃.
Optimized technical scheme, (R)-(+)-3-substituted benzene amino-1, the 2-propylene glycol is 1:1.5 with the ratio of the amount of substance of carbonyl derivative; Used organic solvent is selected from methyl alcohol, ethanol, Virahol, ether, tetrahydrofuran (THF), diisopropyl ether or DMF; Temperature of reaction is-5~5 ℃.
Further technical scheme, (R)-(+)-3-substituted benzene amino-1, in 2-propylene glycol intermediate and the carbonyl derivative VI reaction process, add de-acidying agent, de-acidying agent is selected from mineral alkali or organic bases; The mol ratio of de-acidying agent and intermediate is 0~4:1.
Preferably, de-acidying agent is selected from sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood, sodium bicarbonate, saleratus, pyridine, quinoline or triethylamine; The mol ratio of de-acidying agent and intermediate is 0~2.4:1.
In the technique scheme, according to X
2, X
3It can be halogen, as chlorine, bromine, it also can be the halogen substituted alkoxy, the alkoxyl group of other replacement etc., according to different combinations, described carbonyl derivative is selected from phosgene, two phosgene, triphosgene, methyl-chloroformate, Vinyl chloroformate, propyl chloroformate, butyl chlorocarbonate, chloroformic acid benzyl ester, methylcarbonate, diethyl carbonate, dipropyl carbonate, dibutyl carbonate, phenyl chloroformate, the adjacent chlorobenzene ester of chloroformic acid, chloroformic acid is to the chlorobenzene ester, the chloroformic acid m-chlorophenyl ester, the adjacent bromobenzene ester of chloroformic acid, chloroformic acid is to the bromobenzene ester, chloroformic acid bromochlorophene ester, chloroformic acid ortho-nitrophenyl ester, p-nitrophenyl chloroformate ester, chloroformic acid nitroxyl chloride phenyl ester, diphenyl carbonate, the two adjacent chlorobenzene esters of carbonic acid, the two m-chlorophenyl esters of carbonic acid, carbonic acid biconjugate chlorobenzene ester, the two adjacent bromobenzene esters of carbonic acid, bromobenzene ester between carbonic acid is two, carbonic acid biconjugate bromobenzene ester, the two o-chloronitrobenzene esters of carbonic acid, the two m-nitro esters of carbonic acid, carbonic acid biconjugate nitro phenyl ester or phosphinylidyne diimidazole.
Preferably, described carbonyl derivative is selected from triphosgene, two phosgene, phosgene, chloroformic acid benzyl ester, methyl-chloroformate, Vinyl chloroformate or phosphinylidyne diimidazole.。
In the technique scheme, the reagent Racemic glycidol that uses (structural formula V) be configured as the S configuration, intermediate (R)-(+)-3-substituted benzene amino-1,2-propylene glycol (formula II I) be configured as the R configuration, product 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone (general formula I) be configured as the R configuration.
Product of the present invention is that synthetic Linezolid (Linezolid), thunder get azoles amine (Radezolid), the appropriate useful key intermediate that draws azoles amine (Torarolide), thunder shellfish azoles amine oxazolidine ketone antiseptic-germicides such as (Ranbezolid).
Because technique scheme is used, the present invention compared with prior art has following advantage:
The present invention is raw material with the substituted aniline of formula II, by intermediate (R)-(+)-3-substituted benzene amino-1, the 2-propylene glycol, the method of the 3-substituted-phenyl-5-Qiang Jia Ji oxazolidine-2-ketone of two step prepared in reaction general formula Is and literature method are relatively, it is few to have step, simple to operate, raw material is cheap and easy to get, the reaction conditions gentleness, avoided such as butyllithium, the reagent that potassium tert.-butoxide is such, and very low temperature, absolute anhydrous so harsh reaction conditions, reaction efficiency height not only, energy consumption is low, and improved the safety in production coefficient, reduced production cost, simultaneously, employed reagent atom utilization height in the preparation process of the present invention, the carbon atom utilization ratio reaches 100%, therefore, does not produce organic by-products in the production process, unique side product sodium-chlor, environmental pollution is little.
Therefore, combined coefficient height of the present invention, energy consumption is low, and three-waste pollution is few, is the green synthesis method of a kind of environmental protection close friend, low-carbon (LC).
Embodiment
Be further described below in conjunction with the present invention of embodiment:
Embodiment one:
At 500ml stirring is housed, adds 3-fluoro-4-(4-morpholinyl in the four-hole bottle of condenser and thermometer) aniline 29.4g(0.15mol), (S)-Racemic glycidol 7.4g(0.1mol) and 200ml ethanol, stirring heating backflow 12hrs.
Decompression removes solvent, adds 200ml water, stirs 1hr.Suction filtration gets the aqueous solution of compound (2), can be directly used in down the step ring-closure reaction.Through quantitative analysis, include (R)-(+)-3-(3-fluoro-4-morpholine phenylamino)-1,2-propylene glycol 23.11g.Yield 85.6%.
At 1000ml stirring is housed, adds the about 350ml(0.0854mol of the aqueous solution that includes 23.11g compound (2) in the example 1 in the four-hole bottle of dropping funnel and thermometer), the 100ml ethylene dichloride.Bathe under the cooling at cryosel, control liquid temperature slowly drips the dichloroethane solution 120ml(0.11mol that contains the 11g triphosgene at 0~5 ℃).Drip and finish, at 5 ℃ of following insulated and stirred 1hr.Under this temperature, drip 100g 15% aqueous sodium hydroxide solution then.Drip and finish, be warming up to room temperature, insulated and stirred 2hrs.
Reaction finishes, and standing demix divides and gets organic layer, and water extracts secondary with 150ml * 2 ethylene dichloride.Abandon water, merge organic phase, with the water washing of 100ml saturated common salt once.
Decompression removes ethylene dichloride, takes off to 100ml to add the 200ml aqueous solution that contains 10g 36% hydrochloric acid, continues to remove ethylene dichloride, takes off most solvent, adds proper amount of active carbon, stirs decolouring 1hr.
Suction filtration, the filtering insolubles.Add the 150ml ethylene dichloride in the filtrate, about 10 ℃, transfer solution PH 〉=11 with liquid caustic soda.Stir 30min, standing demix, water extracts secondary with 100ml * 2 ethylene dichloride.Merge organic phase, with the water washing of 100ml saturated common salt once.Decompression removes ethylene dichloride, takes off most ethylene dichloride, and the raffinate recrystallization from ethyl acetate/petroleum ether gets 3-(3-fluoro-4-morpholinyl phenyl)-5-Qiang Jia Ji oxazolidine-2-ketone, canescence crystallization 21g, yield 82.9%.127~129 ℃ of product fusing points, optically-active-55 ° (C=0.99, chloroform).FAB-MSm/z:297.1[M+
](100).?'H-NMR(CDCL3,300MHz)δ:7.43(dd.1H,Ar-H),7.09(dd,!H,Ar-H),6.96(t,1H,Ar-H),4.73(m,3H,H-4-CH
2OH),3.87(t,4H,-CH
2OCH
2-),3.76(d,1H.4-H),3.06(t,4H,-CH
2NCH
2-)。
Embodiment two:
Except replacing the ethanol with Virahol, all the other obtain (R)-(+)-3-(3-fluoro-4-morpholine phenylamino with embodiment one)-1, the aqueous solution of 2-propylene glycol can be directly used in down and go on foot ring-closure reaction.Through quantitative analysis, include (R)-(+)-3-(3-fluoro-4-morpholine phenylamino)-1,2-propylene glycol 19.04g.Yield 70.5%.
Embodiment three:
Except replacing three surpalites with two phosgene, all the other are with embodiment one.Get 3-(3-fluoro-4-morpholinyl phenyl)-5-Qiang Jia Ji oxazolidine-2-ketone, 20g, yield 67.6%.(with (S)-Racemic glycidol).
Embodiment four:
Except replacing three surpalites with the phosphinylidyne diimidazole and not the hydro-oxidation sodium de-acidying agent, all the other are with embodiment one.Get 3-(3-fluoro-4-morpholinyl phenyl)-5-Qiang Jia Ji oxazolidine-2-ketone, 20.86g, yield 70.5%.(in (S)-Racemic glycidol).
Embodiment five:
Except using 3-fluoro-4-(N-tert-butoxycarbonyl-piperazine base) aniline replacement 3-fluoro-4-(4-morpholinyl) aniline, molar ratio is constant, and all the other are with embodiment one.Obtain 3-[ 3-fluoro-4-(N-tert-butoxycarbonyl-piperazine base) phenyl ]-5-Qiang Jia Ji oxazolidine-2-ketone, 27.65g. yield 70%.(in (S)-Racemic glycidol).
Claims (9)
1. the preparation method of 3-substituted-phenyl-5-hydroxyl first base oxazolidine-2-ketone, the structural formula of described 3-substituted-phenyl-5-hydroxyl first base oxazolidine-2-ketone is:
In the formula, R
1Be halogen; R
2Be nitrogen heterocyclic ring or replacement aromatic ring;
Z in the formula
1Be O, S or NR
4, R
4Be amine protecting group;
R
3Alkyl for C1-C4;
R wherein
6Alkyl for C1-C6; R
7Be amine protecting group; R
8Be amine protecting group;
It is characterized in that: the substituted aniline with formula II is raw material,
R in the formula
1, R
2Definition the same,
With Racemic glycidol by synthetic intermediate (R)-(+)-3-substituted benzene amino-1 that obtains of condensation reaction, 2-propylene glycol, the structural formula of described Racemic glycidol be,
Described (R)-(+)-3-substituted benzene amino-1, the structural formula of 2-propylene glycol is,
R in the formula
1, R
2Definition the same,
With the reaction of compound III and carbonyl derivative, namely obtain target compound again, the structural formula of described carbonyl derivative is,
Wherein, X
2, X
3Be leavings group, be selected from C1~C4 alkoxyl group, the benzyloxy of halogen, halogen replacement
,Phenoxy group or imidazolyl that phenoxy group, ortho position or a position or contraposition halogen or nitro replace, X
2, X
3Can be identical, also can be different.
2. according to the preparation method of the described 3-substituted-phenyl of claim 1-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: in described substituted aniline and the Racemic glycidol reaction, substituted aniline is 0.8~5:1 with the ratio of the amount of substance of Racemic glycidol; Used organic solvent is selected from alcohol, ether or methane amide; Temperature of reaction is 20~100 ℃.
3. according to the preparation method of the described 3-substituted-phenyl of claim 2-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: substituted aniline is that the used organic solvent of 0.8~1.5:1 is selected from methyl alcohol, ethanol, Virahol, ether, tetrahydrofuran (THF), diisopropyl ether or DMF with the ratio of the amount of substance of Racemic glycidol; Temperature of reaction is 60~80 ℃.
4. according to the preparation method of the described 3-substituted-phenyl of claim 1-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: (R)-(+)-3-substituted benzene amino-1, the 2-propylene glycol is 1:1~2 with the ratio of the amount of substance of carbonyl derivative; Used organic solvent is selected from alcohol, ether or methane amide; Temperature of reaction is-20~20 ℃.
5. according to the preparation method of the described 3-substituted-phenyl of claim 4-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: (R)-(+)-3-substituted benzene amino-1, the 2-propylene glycol is 1:1.5 with the ratio of the amount of substance of carbonyl derivative; Used organic solvent is selected from methyl alcohol, ethanol, Virahol, ether, tetrahydrofuran (THF), diisopropyl ether or DMF; Temperature of reaction is-5~5 ℃.
6. according to the preparation method of the described 3-substituted-phenyl of claim 1-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: (R)-(+)-3-substituted benzene amino-1, in 2-propylene glycol intermediate and the carbonyl derivative VI reaction process, add de-acidying agent, de-acidying agent is selected from mineral alkali or organic bases; The mol ratio of de-acidying agent and intermediate is 0~4:1.
7. according to the preparation method of the described 3-substituted-phenyl of claim 1-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: de-acidying agent is selected from sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood, sodium bicarbonate, saleratus, pyridine, quinoline or triethylamine; The mol ratio of de-acidying agent and intermediate is 0~2.4:1.
8. according to the preparation method of the described 3-substituted-phenyl of claim 1-5-(R)-Qiang Jia Ji oxazolidine-2-ketone, it is characterized in that: described carbonyl derivative is selected from phosgene, two phosgene, triphosgene, methyl-chloroformate, Vinyl chloroformate, propyl chloroformate, butyl chlorocarbonate, chloroformic acid benzyl ester, methylcarbonate, diethyl carbonate, dipropyl carbonate, dibutyl carbonate, phenyl chloroformate, the adjacent chlorobenzene ester of chloroformic acid, chloroformic acid is to the chlorobenzene ester, the chloroformic acid m-chlorophenyl ester, the adjacent bromobenzene ester of chloroformic acid, chloroformic acid is to the bromobenzene ester, chloroformic acid bromochlorophene ester, chloroformic acid ortho-nitrophenyl ester, p-nitrophenyl chloroformate ester, chloroformic acid nitroxyl chloride phenyl ester, diphenyl carbonate, the two adjacent chlorobenzene esters of carbonic acid, the two m-chlorophenyl esters of carbonic acid, carbonic acid biconjugate chlorobenzene ester, the two adjacent bromobenzene esters of carbonic acid, bromobenzene ester between carbonic acid is two, carbonic acid biconjugate bromobenzene ester, the two o-chloronitrobenzene esters of carbonic acid, the two m-nitro esters of carbonic acid, carbonic acid biconjugate nitro phenyl ester or phosphinylidyne diimidazole.
9. the preparation method of described 3-substituted-phenyl-5-(R)-Qiang Jia Ji oxazolidine-2-ketone according to Claim 8, it is characterized in that: described carbonyl derivative is selected from triphosgene, two phosgene, phosgene, chloroformic acid benzyl ester, methyl-chloroformate, Vinyl chloroformate or phosphinylidyne diimidazole.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2011102007143A CN102311402B (en) | 2011-07-18 | 2011-07-18 | Preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2011102007143A CN102311402B (en) | 2011-07-18 | 2011-07-18 | Preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102311402A CN102311402A (en) | 2012-01-11 |
CN102311402B true CN102311402B (en) | 2013-08-21 |
Family
ID=45425004
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2011102007143A Active CN102311402B (en) | 2011-07-18 | 2011-07-18 | Preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102311402B (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103641790B (en) * | 2013-12-24 | 2015-09-30 | 合肥星宇化学有限责任公司 | The synthetic method of Yi Zhong Evil humulone |
CN112409286B (en) * | 2019-08-20 | 2022-08-05 | 杭州迪克科技有限公司 | Synthesis method of N-substituted phenyl-5-hydroxymethyl-2-oxazolidinone |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4461773A (en) * | 1982-09-15 | 1984-07-24 | E. I. Dupont De Nemours And Company | P-Oxooxazolidinylbenzene compounds as antibacterial agents |
CN1215393A (en) * | 1996-04-11 | 1999-04-28 | 法玛西雅厄普约翰美国公司 | Process to prepare oxazolidinones |
-
2011
- 2011-07-18 CN CN2011102007143A patent/CN102311402B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4461773A (en) * | 1982-09-15 | 1984-07-24 | E. I. Dupont De Nemours And Company | P-Oxooxazolidinylbenzene compounds as antibacterial agents |
CN1215393A (en) * | 1996-04-11 | 1999-04-28 | 法玛西雅厄普约翰美国公司 | Process to prepare oxazolidinones |
Non-Patent Citations (1)
Title |
---|
孟庆国,等.新3,5-二取代噁唑烷酮抗菌剂的合成及其体外抑菌活性.《药学学报》.2003,第38卷(第10期),754-759. * |
Also Published As
Publication number | Publication date |
---|---|
CN102311402A (en) | 2012-01-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1328509B1 (en) | Methods of producing oxazolidinone compounds | |
US11136310B2 (en) | Iminotetrahydropyrimidinone derivatives as plasmepsin V inhibitors | |
CN102827154B (en) | New method for synthesizing rivaroxaban intermediate 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone | |
CN102311402B (en) | Preparation method of 3-substituted phenyl-5-hydroxymethyl oxazolidine-2-ketone | |
EP2838897A1 (en) | Process for the preparation of rivaroxaban and intermediates thereof | |
CN102617501A (en) | Substituted valeramide compound, preparation method and application thereof | |
CN104487436B (en) | Improved process for preparing rivaroxaban using intermediates | |
CN114478690B (en) | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane derivative | |
CN102827199A (en) | Synthetic method for penem and carbapenem antibiotic type key intermediate 4AA | |
CN102321042B (en) | Preparation method of 3-substituted phenyl-5-hydroxymethyloxazolidine-2-ketone | |
CN103304567B (en) | Preparation method of ticagrelor | |
EP3095777B1 (en) | Linezolid intermediate and method for synthesizing linezolid | |
Yan et al. | Synthesis and in vitro antibacterial activity of novel fluoroalkyl-substituted pyrazolyl oxazolidinones | |
US9926283B2 (en) | Intermediate compound for preparing rosuvastatin calcium and method for preparing rosuvastatin calcium therefrom | |
EP2816039B1 (en) | Method for preparing linezolid intermediate | |
CN102070497B (en) | Synthesis method of florfenicol | |
CN105085510A (en) | Preparation method of (S)-4-oxo-2-(thiazolidine-3-carbonyl) pyrrolidone-1-carboxylic acid tert-butyl ester | |
CN104045645B (en) | The synthetic method of harringtonine C ring intermediates | |
CN109851534B (en) | Synthetic method of florfenicol intermediate | |
CN110016024B (en) | Key intermediate for synthesizing CDK4/6 dual inhibitor and preparation method and application thereof | |
US9586913B2 (en) | Processes for the preparation of linezolid using novel intermediates | |
CN102887871B (en) | The preparation method of 3-substituted-phenyl-5-An Jia Ji oxazolidine-2-ketone | |
CN110372640A (en) | A kind of preparation method of 4-AA key intermediate epoxy butyramide | |
WO2014045292A1 (en) | Improved process for the preparation of linezolid intermediate | |
CN105859704A (en) | Method for synthesizing 5-(3-indolyl) oxazole derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |