Cyclopropylacetylene (CA) is a key intermediate in the synthesis for an inhibitor of the HIV reverse transcriptase Efavirenz, an antiviral drug used to treat HIV infections. CA is an expensive raw material, difficult to obtain, and serves of great significance in the preparation of medicaments to combat AIDS. The efficient process for the preparation of CA is described, in which cyclopropyl methyl ketone is chlorinated with PCl5 and the 1,1-dichloro-1-cyclopropylethane isolated, and then dehydrochlorinated with potassium tert-butoxide in toluene to form CA. However, the aforementioned chlorination protocol was found to take place with appreciable opening of the cyclopropyl ring. In order to suppress this during chlorination, the employment of dichlorotriphenylphosphorane–Ph3PCl2–as a mild chlorinating agent is predicted to give a mixture of 1-chloro-1- cyclopropylethene and I,I-dichloro-1-cycloproplehtane. Subsequent treatment with a strong base is expected produce the title compound at higher yields with significant reduction in ring opening. Additional synthetic routes will also be presented.

Efficient synthesis of cyclopropylacetylene, a crucial synthetic intermediate for efavirenz using chlorinating reagents ( PCl5 and Ph3PCl2)

ACS Spring 2022

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