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US 6,028,237 AGranted
Synthesis of cyclopropylacetylene
AssigneeDuPont Pharmaceuticals Company
InventorRodney Lawrence Parsons, Jr.
Life of this patent
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Abstract
The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is a reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-ben zoxazin-2-one which is a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
Claims19
A process for synthesis of cyclopropylacetylene, said process comprising:
- (1) contacting 5-halo-1-pentyne with a suitable strong base to form a reaction mixture and effect formation of cyclopropylacetylide;
- (2) adding a concentration solvent;
- (3) distilling the reaction mixture under vacuum to reduce the volume;
- and
- (4) contacting the reaction mixture with a suitable quenching agent to effect formation of cyclopropylacetylene.
2 more elements
A process for synthesis of cyclopropylacetylene, said process comprising:
- (1) contacting one equivalent of 5-chloro-1-pentyne with about two to about three equivalents of a n-hexyllithium in either tetrahydrofuran or a combination of tetrahydrofuran/hexane at a temperature of between about -10.degree. C. and about 30.degree. C. for sufficient time to form a reaction mixture and effect greater than about 95% formation of cyclopropylacetylide;
- (2) adding toluene;
- (3) distilling the reaction mixture under vacuum at a temperature of between about 20.degree. C. and about 65.degree. C. to reduce the volume to about one third the volume before distillation under vacuum;
- (4) contacting the reaction mixture with a ammonium chloride to effect formation of cyclopropylacetylene;
- (5) drying the reaction mixture to a water content of between about 1 to about 400 parts per million;
- and
- (6) purifying the desired product by distillation.
4 more elements
Dependencies are inferred from the claim text.