Practical asymmetric synthesis of efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor

…, YS Lo, S Silverman, JR Moore, Q Islam…

Index: Pierce, Michael E.; Parsons Jr., Rodney L.; Radesca, Lilian A.; Lo, Young S.; Silverman, Stuart; Moore, James R.; Islam, Qamrul; Choudhury, Anusuya; Fortunak, Joseph M. D.; Nguyen, Dieu; Luo, Chi; Morgan, Susan J.; Davis, Wayne P.; Confalone, Pat N.; Chen, Cheng-Yi; Tillyer, Richard D.; Frey, Lisa; Tan, Lushi; Xu, Feng; Zhao, Dalian; Thompson, Andrew S.; Corley, Edward G.; Grabowski, Edward J. J.; Reamer, Robert; Reider, Paul J. Journal of Organic Chemistry, 1998 , vol. 63, # 23 p. 8536 - 8543

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Citation Number: 179

Abstract

A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4- chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1 R, 2 S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) ...