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Industrial production process of palmitate of clindamycin hydrochloride

A technology of clindamycin hydrochloride and palmitate, applied in the directions of sugar derivatives, organic chemistry, carbohydrate active ingredients, etc., can solve the problems of high toxicity, difficulty in industrialized large-scale production, and high price of anisaldehyde, and achieves process conditions. Gentle, energy-saving effect

Active Publication Date: 2008-02-13
重庆凯林制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The disadvantages of the above method are: 1. The process of using anisaldehyde as a protective agent requires water separation and anisaldehyde is expensive
2. A large amount of highly toxic acetonitrile was used in the British patent precipitation product
3. Regardless of whether it is filtered under nitrogen protection or spray-dried to obtain finished products, it is not easy to industrialize large-scale production
4. The finished product is difficult to dry and needs to be dried in the presence of nitrogen flow or vacuum, and the purity of the finished product is low, HPLC is only 93%
Therefore above-mentioned method has certain difficulty in industrial implementation

Method used

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  • Industrial production process of palmitate of clindamycin hydrochloride
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  • Industrial production process of palmitate of clindamycin hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Add 19.8kg of clindamycin hydrochloride isopropylidene and 200kg of chloroform into the reaction kettle, cool to 0°C with ice water, and add 17.5kg of palmitoyl chloride dropwise. After dropping, add 3kg triethylamine. React at 18°C ​​for 30 minutes, then raise the temperature to 35°C and react for 3 hours to obtain about 25.0 kg of clindamycin palmitate isopropylidene hydrochloride.

[0029] Add 80kg of water to clindamycin hydrochloride palmitate isopropylidene, stir for 10min, and extract with chloroform for 3 times. Combine the organic phases, evaporate the solvent under vacuum at 0.085 MPa, add 90 kg of ethanol to the residue and reflux for 1 hour, then evaporate under vacuum at 0.085 MPa to obtain the crude clindamycin palmitate hydrochloride.

[0030] The crude product of clindamycin palmitate hydrochloride was refluxed and dissolved with 50 kg of isopropanol, the solvent was evaporated, and 78 kg of acetone was added to the residue. Stir at 40°C for 2.5 hours,...

Embodiment 2

[0032] Add 19.8kg of clindamycin hydrochloride isopropylidene and 200kg of chloroform into the reaction kettle, cool to 0°C with ice water, and add 17.5kg of palmitoyl chloride dropwise. After dropping, add 3kg of 2-picoline. React at 18°C ​​for 30 minutes, then raise the temperature to 35°C and react for 3 hours to obtain about 25.0 kg of clindamycin palmitate isopropylidene hydrochloride.

[0033] Add 90kg of water to clindamycin hydrochloride palmitate isopropylidene, stir for 10min, and extract with n-hexane for 3 times. Combine the organic phases, evaporate the solvent to dryness under vacuum at 0.082 MPa, add 85 kg of ethanol to the residue and reflux for 1 hour, then evaporate to dryness under vacuum at 0.082 MPa to obtain the crude product of clindamycin palmitate hydrochloride.

[0034] The crude product of clindamycin palmitate hydrochloride was refluxed and dissolved with 48kg of isopropanol, the solvent was evaporated, and 78kg of acetone was added to the residue....

Embodiment 3

[0036] Add 19.8kg of clindamycin hydrochloride isopropylidene and 200kg of chloroform into the reaction kettle, cool to 0°C with ice water, and add 17.5kg of palmitoyl chloride dropwise. After dropping, add 3kg of K 2 CO 3 . React at 18°C ​​for 30 minutes, then raise the temperature to 35°C and react for 3 hours to obtain about 25.0 kg of clindamycin palmitate isopropylidene hydrochloride.

[0037] Add 85kg of water to clindamycin hydrochloride palmitate isopropylidene, stir for 10min, and extract twice with chloroform. Combine the organic phases, evaporate the solvent to dryness under vacuum at 0.082 MPa, add 85 kg of ethanol to the residue and reflux for 1 hour, then evaporate to dryness under vacuum at 0.082 MPa to obtain the crude product of clindamycin palmitate hydrochloride.

[0038] The crude product of clindamycin palmitate hydrochloride was refluxed and dissolved with 50 kg of isopropanol, the solvent was evaporated, and 78 kg of acetone was added to the residue. ...

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Abstract

The industrial production process of palmitate of clindamycin hydrochloride includes the following main steps: the reaction of isopropylylidene clindamycin hydrochloride and palmitoyl chloride in the presence of acid-binding agent to prepare palmitate of isopropylylidene clindamycin hydrochloride; eliminating protecting radical to obtain coarse palmitate of clindamycin hydrochloride; and final re-crystallization and separation to obtain palmitate of clindamycin hydrochloride product. The present invention has the advantages of facile materials, simple and mild technological process and low power consumption, can obtain white product with HPLC content up to 97.1 %, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of clindamycin palmitate hydrochloride, in particular, a method for industrial production of clindamycin palmitate hydrochloride. Background technique [0002] Clindamycin hydrochloride palmitate is the main raw material for the production of antibiotic clindamycin hydrochloride palmitate dispersible tablets, dry syrup, granules and other dosage forms. Its structural formula is: [0003] [0004] British Patent GB1205083 discloses a method for preparing clindamycin palmitate hydrochloride, which uses anisaldehyde as a protective agent and clindamycin hydrochloride to reflux and separate water to prepare clindamycin hydrochloride protected by 3 and 4 hydroxyl groups The mycin is then reacted with palmitoyl chloride, hydrolyzed and deprotected to prepare clindamycin palmitate hydrochloride. In this patent, when the final product is obtained, the reaction residue is dissolved in acetone, the resulting sol...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/16A61K31/70A61P31/00
Inventor 龙道兵程秀华莫启壮郭钱浩彭良臣
Owner 重庆凯林制药有限公司
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