Abstract

Objectives: To optimize the synthesis process of memantine hydrochloride by direct aminoation of 1-bromo-3,5-dimethyladamantane with urea. Materials and methods: Using the basic chemical reactions to optimize the reaction conditions. Results: The optimal conditions of the memantine hydrochloride synthesis process include: The reaction solution was diphenyl ether; the reaction temperature was 170oC within 4 hours (in the first step) and 100oC within 2 hours (in the second step); the molar ration of 1-bromo-3,5-dimethyladmantane: urea: diphenyl ether was 1:3:2.5; the duration of the reaction was 6 hours and the overall yields were 75.81%. Conclusion: The synthesis process of memantine hydrochloride by direct aminoation with urea was established. The finished products were determined by IR, MS, and NMR spectra and met the standards of USP 43.

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