tert-Butyl acrylate → (1R*,5S*,6RS)-8-Benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one

Participants

Reaction Steps

A mixture of N-benzyl-3-hydroxy-2-phenylpyridinium bromide (255 g, 0.745 mol), tert-butyl acrylate (470 ml), triethylamine (150 ml) and 1,4-dioxane (1 l) was heated at reflux for 15 hours and cooled to room temperature. The reaction mixture was poured onto saturated aqueous NaHCO3 (1 l) and extracted into an 1:1 mixture of iso-hexane:diethyl ether (3×500 ml). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (750 g, iso-hexane:diethyl ether 0-20%) to give a 2:1 mixture of (1R*,5S*,6R*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one and (1R*,5S*,6S*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one (205 g, 70%) as a yellow-orange foam. The isomers were separated on silica gel (iso-hexane:diethyl ether) and crystallised from iso-hexane:diethyl ether giving yellow rhombs:

Provenance & Evidence