Cyclopropylacetylene → (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide

Participants

Reaction Steps

2.5M n-Butyllithium (2.05 mL, 5.14 mmol) was added slowly to a solution of cyclopropyl acetylene (0.34 g, 5.14 mmol) in tetrahydrofuran (4 mL) in an ice-salt-bath under argon, and then N,N-bis((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl)-4-chloro-2-(2,2,2-trifluoroacetyl)aniline (11, 1 g, 1.71 mmol) in THF (2 mL) was added. The reaction mixture was stirred for 1 hour. The reaction was quenched with 10% citric acid aqueous, the mixture was extracted with ethyl acetate and the two layers were separated. The organic layer was evaporated to dryness to give a crude oil and further crystallized with ethyl acetate and petroleum ether to give pure (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (10).

Provenance & Evidence