The Ruppert–Prakash reagent is the most powerful and well-documented reagent for trifluoromethylation. Despite its versatility, no general method exists for its use in a flow system. Here we report the first flow trifluoromethylation of carbonylcompounds and its utility for drug synthesis of efavirenz and HSD-016, including preliminary results of enantioselective variants.
[EN] PROCESS FOR PREPARATION OF EFAVIRENZ BY CYCLISATION<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ÉFAVIRENZ PAR CYCLISATION
申请人:LONZA AG
公开号:WO2012097510A1
公开(公告)日:2012-07-26
The invention disclosed a process for the preparation of the HIV drug Efavirenz, also known as DMP-266, starting from 1,4-dichlorobenzene, and its intermediates.
Efavirenz is manufactured worldwide, and its asymmetric synthesis requires a complex organometallic approach, while an organocatalytic approach is far less efficient. The first highly enantioselective approach is disclosed for the synthesis of Efavirenz under nonmetal organocatalysis with up to 93% ee for the Merck intermediate and 91% ee for the Lonsa intermediate using novel alkynyl cinchona catalysts
Catalytic Enantioselective Synthesis of Key Propargylic Alcohol Intermediates of the Anti-HIV Drug Efavirenz
作者:Yu Zheng、Lilu Zhang、Eric Meggers
DOI:10.1021/acs.oprd.7b00376
日期:2018.1.19
The catalytic, enantioselectivesynthesis of key propargylic alcohol intermediates toward the synthesis of the anti-HIV drug efavirenz is reported. Using a recently reported chiral-at-ruthenium catalyst ( J. Am. Chem. Soc. 2017, 139, 4322), catalyticenantioselective alkynylations of 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethanone (99% yield, 95% ee) and 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone