Efavirenz is used in the treatment of AIDS, however, the inaccessibility of efavirenz to millions of people worldwide, prompted us to develop a more efficient process in classic batch chemistry as well as further optimizing all process parameters by incorporating a semi continuous flow protocol. Based on the advantages that continuous flow reactors present, we investigated the preparation of efavirenz using a semi-continuous flow protocol in an attempt to meet the rising global needs for life-saving medicine. A novel four step process starting from 4-chloroaniline, which undergoes trifluoroacetylation, an addition of cyclopropyl acetylene in the presence of a chiral axillary and finally cyclization in the presence of diethyl carbonate to afforded efavirenz with 99% optical purity. The key intermediate was established in the presence of n-BuLi, previously reported only with sec-BuLi or t-BuLi. This streamlined process provides the shortest synthesis method for the preparation of efavirenz. Although there are several methods reported for the synthesis of efavirenz, we synthesized and patented an efficient route, which is suitable for large-scale synthesis to support the development of these compounds. In this process, we successfully prepared one of the intermediates of efavirenz without using any solvents, thus promoting green synthesis.

New synthetic route for the preparation of efavirenz

254th National Meeting (2017)

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