Preparation method of clindamycin phosphate

Abstract

The invention belongs to the technical field of chemical synthesis and relates to a preparation method of clindamycin phosphate. The preparation method includes preparing clindamycin isopropylidene alkali from clindamycin hydrochloride monohydrate, subjecting the clindamycin isopropylidene alkali to phosphate esterification with phosphorus oxychloride as a phosphate esterification agent and 1,2,4-triazole as an acid-binding agent to obtain isopropylidene clindamycin phosphate, and subjecting the isopropylidene clindamycin phosphate to deprotection by hydrolysis of mixed acid to obtain the clindamycin phosphate. The preparation method has the advantages that by preparing the clindamycin phosphate through one-step hydrolysis of organic acid, the preparation method is energy saving and environment friendly; the preparation method is high in yield and low in cost and can obtain the high-purity finished product directly without subsequent refining, so that the molar yield of the clindamycinphosphate can reach 96.15%; the clindamycin phosphate is good in crystal form (bulk density and liquidity), so that aseptic packaging is benefited.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis and relates to a preparation method of clindamycin phosphate. Background technique [0002] Clindamycin Phosphate, chemical name 6(1-methyl-trans-4-propyl-L-pyrrolidinecarboxamido)-1-thio-7(s)-chloro-6 , 7,8-trideoxy-L-threo-a-D-galactopyranoside-2-phosphate, white crystalline powder, hygroscopic, easily soluble in water, slightly soluble in methanol, in ethanol, Almost insoluble in acetone. Its structural formula is: [0003] [0004] Clindamycin phosphate is widely used clinically. It is a derivative of lincomycin hydrochloride and belongs to antibiotic drugs. The mechanism of action is to inhibit bacterial protein synthesis. Its antibacterial spectrum is the same as that of lincomycin, and it is effective against Gram-positive bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus hemolyticus, Streptococcus viridans, Pneumococcus pneumoniae, and Bacil...

AI Technical Summary

Problems solved by technology

However, the phosgene produced by solid phosgene under the decomposition of DMF is highly toxic. There have been many vicious accidents in my country where phosgene leaked from companies using solid phosgene and caused death.

The reason for the leakage lies in the process of preparing the solid phosgene solution. The process used by the manufacturer is to first dissolve the solid phosgene in chloroform in the open field, and after fully dissolving, the trichloromethane dissolved in the solid phosgene The methane solution is transferred to the solvent tank with a solvent pipe and transported to the production workshop, and then the chloroform solution dissolved in solid phosgene is vacuum filtered into the high level tank, and the chloroform solution dissolved in solid phosgene is filtered through the pipeline Add it dropwise into a DMF reactor to form a chlorinated reagent. During the whole process, there are many and frequent material transfers and drops, and the chloroform solution dissolved in solid phosgene is in the state of being heated and wet during the transfer process. It is easy to decompose and produce phosgene, which is easy to cause leakage, cause phosgene volatilization and cause poisoning incidents, and there are great safety hazards in operation

Images