Synthesis method of bupivacaine

Abstract

The invention belongs to a synthesis method of bupivacaine. The method comprises: adding 2 piperidinecarboxylicacid into aqueous alkali, dropwise adding Cbz and alkaline water, after finishing dropwise adding at normal temperature, reacting for 12 hours, after reaction, extracting with diethyl ether, washing a water layer to be weak-acid with 18% of diluted hydrochloric acid, extracting with the diethyl ether again, combining an diethyl ether layer, drying and filtering, and concentrating to obtain a dried product; adding the dried product into a DMF solvent, then adding a catalyst for reaction for 1 hour at normal temperature, then adding 2,6-dimethylaniline, reacting for 18hours at normal temperature, adding water and ethyl acetate for washing, taking an organic layer, drying and filtering, and concentrating to obtain a dried concentrated product; adding the dried concentrated product into a solvent, then adding a catalyst, pressurizing and introducing hydrogen, filtering after reaction and concentrating to obtain a dried product; adding the product in the above step into a solvent, dropwise adding bromo-n-butane at normal temperature, after dropwise adding, rising temperature to 80 DEG C for reacting for 12 hours, adding diluted hydrochloric acid, slowing cooling to normal temperature, and crystallizing, filtering and drying to obtain the product. The synthesis method has the advantages of higher yield, smaller pollution and low equipment requirement.

Description

technical field [0001] The invention relates to the field of bupivacaine production, in particular to a method for synthesizing bupivacaine. Background technique [0002] Bupivacaine, a long-acting amide local anesthetic, is suitable for peripheral nerve block, epidural block and subarachnoid block. Its hydrochloride is often used as a white crystalline powder, odorless and bitter. Local anesthesia is stronger than lidocaine (about 4 times stronger). Its 0.25% to 0.5% solution generally takes 4 to 10 minutes to cause local anesthesia, and the 0.75% solution takes effect slightly faster. Using its 0.5% solution plus epinephrine for epidural anesthesia, the effect can be maintained for 5 hours. Due to the low concentration of this product in the blood, less accumulation in the body, and a long duration of action, it is a relatively safe long-acting local anesthetic. Existing bupivacaine synthetic method: [0003] . [0004] The disadvantage of the existing method is ...

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Problems solved by technology

[0004] The disadvantages of the existing method: the starting material is caprolactam through ring-opening, bromination, acid chloride, condensation, cyclization, and refining to obtain the finished product bupivacaine, which has low yield, serious pollution, and high requirements for equipment corrosion resistance, etc. shortcoming