CN1355170A - Process for preparing clindamycin-2-benzyl phosphate - Google Patents
Process for preparing clindamycin-2-benzyl phosphate Download PDFInfo
- Publication number
- CN1355170A CN1355170A CN 00134259 CN00134259A CN1355170A CN 1355170 A CN1355170 A CN 1355170A CN 00134259 CN00134259 CN 00134259 CN 00134259 A CN00134259 A CN 00134259A CN 1355170 A CN1355170 A CN 1355170A
- Authority
- CN
- China
- Prior art keywords
- clindamycin
- acid
- benzyl phosphate
- phosphate ester
- alkali
- 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.)
- Granted
Links
Abstract
The present invention relates to a novel process for preparing clindamycin-2-benzyl phosphate which is an intermediate for preparing clindamycin phosphate as antibiotic.
Description
The present invention relates to the new preparation process of clindamycin-2-benzyl phosphate ester.Clindamycin-2-benzyl phosphate ester is the useful as intermediates of preparation antibiotic Clindamycin Phosphate.
United States Patent (USP) 4,849,515 (1989) have disclosed a kind of method for preparing clindamycin-2-benzyl phosphate ester, and it comprises with formula I ketal clindamycin-2-benzyl phosphate ester hydrochloride
R=wherein
Heat in methyl alcohol with aqueous hydrochloric acid, thin up precipitates to producing then, the concentrating part solvent, and the clindamycin benzyl phosphate ester hydrochloride of cooling back filter collection formula II deprotection base, wherein R as above defines.
Use in the alkali again and formula II hydrochloride, go out formula III clindamycin-2-benzyl phosphate ester with dilute hydrochloric acid precipitated at last, wherein R as above defines.
Though this method can prepare clindamycin-2-benzyl phosphate ester, reactions steps is more, and aftertreatment is cumbersome, easily causes the reduction of productive rate and purity.Therefore the new preparation process of seeking clindamycin-2-benzyl phosphate ester is necessary.
The inventor after deliberation, now unexpectedly find to prepare in a step method of the clindamycin-2-benzyl phosphate ester of high purity and high yield, this method comprises formula I ketal clindamycin-2-benzyl phosphate ester hydrochloride is dissolved in the alkali earlier, in same reaction vessel, add excess acid then, reaction solution is after the reaction for some time of heating down, aqueous precipitation goes out solid and is clindamycin-2-benzyl phosphate ester, the present invention is based on above-mentioned discovery and is accomplished.
According to the present invention, used alkali comprises mineral alkali or organic bases among the present invention, as ammoniacal liquor, and alkaline carbonate or supercarbonate, C
1-6Kiber alkyl amine, secondary amine or tertiary amine, alkali metal alcoholate or pyridine etc.Preferred ammoniacal liquor.
According to the present invention, used acid comprises mineral acid or organic acid among the present invention, as dilute phosphoric acid, and formic acid, acetate, propionic acid, butyric acid, phenylformic acid etc., preferred acetate.
According to a preferred embodiment of the invention, the preparation method of clindamycin of the present invention-2-benzyl phosphate ester comprises: ketal clindamycin-2-benzyl phosphate ester hydrochloride is dissolved in the proper ammonia, toward wherein adding excessive acetic acid, reaction solution is after warm for some time, adds depositing in water and goes out solid and be clindamycin-2-benzyl phosphate ester.
The following examples are used for further specifying the present invention, but do not mean that any restriction to the present invention.
Embodiment 1: the preparation of clindamycin-2-benzyl phosphate ester
Get ketal clindamycin-2-benzyl phosphate ester hydrochloride 3g and be dissolved in ammoniacal liquor (dense NH
4OH4ml and water 10ml).Add anhydrous acetic acid 13ml.Stir evenly in bathing 80～90 ℃ of heating of temperature 1 hour.Cooling back thin up is put slightly.The filter collection, washing and drying.Get 218 ℃ of 2.5g (productive rate 94%) m.p.
Ultimate analysis: C
25H
41ClN
2O
8SP3H
2O (645.6).
Calculated value %C46.47; H7.28; N4.34
Measured value %C46.32; H6.45; N4.72
1HNMR(CD
3OD)δ?7.2-7.42(5H，m，Ph-H)，5.42(1H，d，CONH)，5.10(2H，m，ArCH
2O)，4.1-4.8(5H，m，5OCH
-)，3.88(1H，m，R-CHCl)，3.75(2H，m，2NCH
-)，2.2-2.4(3H，m，N-CH
3)，2.08(3H，S，S-CH
3)，0.9(3H，t，CH
2CH
3)，1.25(3H，m，CH
3CHCl)，1.43(6H，m，3HCH
2)。
Claims (4)
1. the preparation method of clindamycin-2-benzyl phosphate ester, it comprises ketal clindamycin-2-benzyl phosphate ester is dissolved in and is selected from ammoniacal liquor, alkaline carbonate or supercarbonate, C
1-6Alkyl primary, the second month in a season or acid amide, basic metal C
1-6In the alkali of alkyl alcoholate or pyridine, be selected from dilute phosphoric acid, formic acid, acetate, propionic acid or benzoic acid toward wherein adding.
2. the process of claim 1 wherein that used alkali is ammoniacal liquor.
3. the process of claim 1 wherein that used acid is acetate.
4. the process of claim 1 wherein that used alkali is ammoniacal liquor, used acid is acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001342592A CN1148376C (en) | 2000-11-29 | 2000-11-29 | Process for preparing clindamycin-2-benzyl phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001342592A CN1148376C (en) | 2000-11-29 | 2000-11-29 | Process for preparing clindamycin-2-benzyl phosphate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1355170A true CN1355170A (en) | 2002-06-26 |
| CN1148376C CN1148376C (en) | 2004-05-05 |
Family
ID=4596131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB001342592A Expired - Fee Related CN1148376C (en) | 2000-11-29 | 2000-11-29 | Process for preparing clindamycin-2-benzyl phosphate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1148376C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115141234A (en) * | 2022-07-14 | 2022-10-04 | 湖南恒生制药股份有限公司 | Synthesis process of clindamycin phosphate raw material medicine |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332967C (en) * | 2004-07-23 | 2007-08-22 | 南阳市鹿城生化研究所 | Clindamycin palmitate hydrochloric acid preparation method |
-
2000
- 2000-11-29 CN CNB001342592A patent/CN1148376C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115141234A (en) * | 2022-07-14 | 2022-10-04 | 湖南恒生制药股份有限公司 | Synthesis process of clindamycin phosphate raw material medicine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1148376C (en) | 2004-05-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4681617B2 (en) | Synthesis of himbacine analogs | |
| US6649796B2 (en) | Process for the preparation of acetamide derivatives | |
| JP2753659B2 (en) | Pyrazole derivatives | |
| CN1148376C (en) | Process for preparing clindamycin-2-benzyl phosphate | |
| US7626045B2 (en) | Synthesis of himbacine analogs | |
| US20090171084A1 (en) | Production method of aminopyrimidine compound | |
| JP2003519677A (en) | Method for producing N-methyl-N'-nitroguanidine | |
| US20040010146A1 (en) | Process for the preparation imidazo[1,2-A]pyridine-3-acetamides | |
| CN109678701A (en) | A kind of preparation method of Vilantro intermediate | |
| KR890001241B1 (en) | Process for preparing 4-acetyl isoquinolinone | |
| JP5919270B2 (en) | Method for producing dimiracetam | |
| KR100522246B1 (en) | Method for preparing di-cycloserine | |
| WO1991001315A1 (en) | New quinoline derivatives and process for the preparation thereof | |
| JP3037024B2 (en) | 5-acyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2-carboxylic acid derivative and method for producing the same | |
| KR100413172B1 (en) | A process for the preparation of quinolinone derivatives | |
| JP2959811B2 (en) | Manufacturing method of acid chloride | |
| KR100277510B1 (en) | Method for preparing tetrahydrocarbazolone derivative | |
| JPS6310143B2 (en) | ||
| JP2001508455A (en) | Method for producing acylated α-aminocarboxylic acid amide | |
| CN113072464A (en) | Simple and convenient teriflunomide preparation method | |
| JPH0525111A (en) | Production of aliphatic amide or its salt | |
| CN106632332A (en) | Novel preparation method for Istradefylline | |
| AU6072590A (en) | New quinoline derivatives and process for the preparation thereof | |
| JPS63216861A (en) | Production of 4-hydroxyindolines | |
| JP2003113181A (en) | Method for producing 6-halopurine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |