The enzymatic resolution of 1‐(4‐chlorophenyl)ethylamine by Novozym 435 to prepare a novel triazolopyrimidine herbicide

• Published in: Chirality
• Main Authors: Zhang, Yinjun, Cheng, Feifei, Yan, Hongde, Zheng, Jianyong, Wang, Zhao
• Other Authors: Natural Science Foundation of Zhejiang Province
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2018
• Subjects: Organic Chemistry; Spectroscopy; Drug Discovery; Pharmacology; Catalysis; Analytical Chemistry; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/chir.23016; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fchir.23016; https://onlinelibrary.wiley.com/doi/pdf/10.1002/chir.23016

Abstract The kinetic resolution of (R,S)‐1‐(4‐chlorophenyl)ethylamine was accomplished using a commercial lipase from Candida antarctica (Novozym 435). The performance of this lipase was investigated for the enantioselective amidation of (R,S)‐1‐(4‐chlorophenyl)ethylamine, leaving the target product (S)‐1‐(4‐chlorophenyl)ethylamine in its unreacted form. The effects of various types of solvents and an acyl donor, the molar ratio of the substrate to the acyl donor, and the reaction temperature were studied. The optimum reaction conditions were found to result in amidation with methyl 2‐tetrahydrofuroate at 40°C in methyl tert‐butyl ether, with a substrate/acyl donor molar ratio of 1:2.4. The conversion rate of (R,S)‐1‐(4‐chlorophenyl)ethylamine was 52%, with an enantiomeric excess of 99% towards the unreacted substrate in a reaction time of 22 hours. Finally, using optically pure (S)‐1‐(4‐chlorophenyl)ethylamine as the raw material, the chemical synthesis of (S)‐N‐(1‐(4‐chlorphenyl)ethyl)‐2‐(5,7‐dimethyl‐[1,2,4]triazolo[1,5‐a]pyrimidin‐2‐ylthio)acetamide, a novel triazolopyrimidine herbicide, was achieved, and the total yield and purity were 83.5% and 95.3%, respectively.