Cerium(III) chloride → (1R*,2S*,5S*,6R*)-8-Benzyl-2-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)ethynyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol

Participants

Reaction Conditions

Reaction Steps

A solution of n-butyl lithium in hexanes (1.6M, 5 ml, 8 mmol) was added dropwise to a stirred solution of 2-cyclopropyloxy-5-trifluoromethoxyphenylethyne (Description 4; 2.0 g, 8.2 mmol) in tetrahydrofuran (30 ml) at −78° C. to form an orange solution that turned violet at the end of addition. The mixture was stirred for 10 minutes and solid anhydrous cerium(III) chloride (2 g, 8.1 mmol) was added. The mixture was stirred for 30 minutes at −78° C. and a solution of (1R*,5S*,6R*)-8-benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-one (Description 7; 2.9 g, 6.7 mmol) in tetrahydrofuran (25 ml) was added dropwise. The reaction mixture was warmed to 0° C. over 30 minutes, stirred at 0° C. for 15 minutes, quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate) to give the title compound (2.4 g, 53%) which was recrystallised from ethyl acetate:iso-hexane.

Provenance & Evidence