Improvements on the Synthesis of Tetracaine Hydrochloride
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R625

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Project Foundation of Chongqing Municipal Education Committee (No.KJ1505501)

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    Abstract:

    Tetracaine hydrochloride was synthesized from N-alkylation,hydrolysis and esterification through three-step reactions,The yield of tetracaine hydrochloride was up to 85.09 %. FTIR,1HNMR and HPLC were used to characterize and analyze the structure and purity of the products.The reaction conditions were optimized, which was studied with the reaction of N-alkylation,hydrolysis and esterification. The results show that,tetracaine hydrochloride is successfully synthesized. The optimal process conditions of N-alkylation, under which the yield of ethyl 4-(butylamino) benzoate( I) is up to 75.69%, are as follows: at 60℃, and with the ratio of triethylamine, benzocaine and 1- bromobutane is 1.2:1:4.6. Compared with the present technology route,the new method has successed in reducing the formation of dibutyl by-product, during formed the key intermediate of ethyl 4-(butylamino)benzoate(I). The optimal synthesis conditions of hydrolysis, are as follows: at 50℃, and with the ratio of sodium hydroxide and ethyl 4-(butylamino)benzoate is 1.4:1. We can get the target product in 8 hours. The production of 4-(butylamino)benzoic acid (Ⅱ)with a 99.78% yield. The optimal reaction conditions of esterification, are as follows: at 116℃, and with the ratio of 2-dimethylaminoethyl chloride hydrochloride and 4-(butylamino)benzoic acid is 1.3:1. The solvent methyl isobutyl ketone ensures the production of tetracaine hydrochloride with a 85.09% yield.

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History
  • Received:June 12,2016
  • Revised:August 08,2017
  • Adopted:August 23,2017
  • Online: February 06,2018
  • Published:
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