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NameMrs. Zully Beck
Organization or InstitutionSoutheastern University
TopicOrganic Chemistry

Efficient synthesis of cyclopropylacetylene, a crucial synthetic intermediate for Efavirenz using chlorinating reagents (PCland Ph3PCl2)


Zully A. Beck, Emily Hutchinson, Michael Siekman, Elizabeth Sanchez Bautista, Brandon Montes, Jessica Echevarria, and Ralph N. Salvatore

Author Institution(s)

Southeastern University


Cyclopropylacetylene (CA) is a key intermediate in the synthesis for the HIV reverse transcriptase inhibitor Efavirenz, an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, employed 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. The resulting 1,1-dichloro-1-cyclopropylethane is isolated and then dehydrochlorinated with potassium tert-butoxide in toluene to form CA.  However, the chlorination protocol has been found to take place with appreciable cyclopropyl ring opening. A mild chlorinating reagent is predicted to reduce ring-opening side products. For this, a one-pot synthesis was employed using dichlorotriphenylphosphorane–Ph3PCl2–as the mild chlorinating agent. This route resulted in 1,1-dichloro-1-cyclopropylethane, and after further treatment with a strong base, CA was produced. Additional synthetic routes will also be presented.