Citation

Wu C, Li Z, Wang C, Zhou Y, Sun T. Organic Process Research and Development 2018; 22(9): 1081-1085.

Copyright

(Copyright © 2018)

DOI

10.1021/acs.oprd.8b00070

PMID

unavailable

Abstract

When preparing lafutidine, we found that the main impurity was dihydrolafutidine. On the basis of the chemical structure of dihydrolafutidine and the mechanism of its production, we decided to use a "suicide substrate" in the drug preparation to increase the purity of lafutidine. By calculating the energy barrier of the reduction reaction with a quantum-chemical method and evaluating the appropriate physicochemical properties of the terminal olefins, we chose 1-hexene as the suicide substrate to effectively control the formation of dihydrolafutidine in the synthesis of lafutidine. The experimental results showed that the content of the impurity, dihydrolafutidine, decreased from 1.5% to less than 0.05%, proving that using a suicide substrate is an effective method to reduce the formation of the relevant byproduct in drug production. In addition, this method is operationally simple and is suitable for industrial applications. © 2018 American Chemical Society.

Language: en

Keywords

Substrates; dihydrolafutidine; Drug preparation; Drug production; Increase the purities; lafutidine; Lafutidine; Physicochemical property; Quantum chemistry; Quantum-chemical methods; Reduction reaction; suicide materials; terminal olefins; Terminal olefins