Dupont Pharmaceuticals Company

Other

Silvio Campagna

Zhe Wang

Pasquale N Confalone

Fuqiang Jin

Roberta L Dorow

Joseph M Fortunak

Jianguo Yin

Process for the preparation of macrocyclic metalloprotease inhibitors

The present invention is directed to a process for the preparation of a compound of formula (X-a):

The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, for example, cyclopropane carboxaldehyde is alkylated to form 1,1,1-trichloro-2-cyclopropyl-ethanol; which in turn is hydroxy protected to form 1,1,1-trichloro-2-cyclopropylethyltosylate; which in turn undergoes elimination to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.

Process for the preparation of cyclopropylacetylene

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New Castle, DE, United States of America

Silvio Campagna