Lithium Chloride → (1R*,2R*,4'S*,5R*)-8-Benzyl-2',3',4',5'-tetrahydro-4'-[(2RS)-2,3-dihydro-2-methyl-5-trifluoromethoxybenzofuran-7-yl]-1-phenyl-6-phenylsulphonylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]

Participants

Reaction Steps

A mixture of (1R*,2R*,5S*,6R*)-8-benzyl-1-phenyl-6-phenylsulphonylspiro[8-azabicyclo[3.2.1]octane-2,2′(5′H)-furan] (Description 15; 500 mg, 1.05 mmol), 2,3-dihydro-7-iodo-2-methyl-5-trifluoromethoxybenzofuran (Description 22; 1.11 g, 3.22 mmol), tetra-n-butylammonium chloride (310 mg, 0.96 mmol), lithium chloride (640 mg, 1.48 mmol), potassium formate (420 mg, 5 mmol), palladium(II) acetate (47 mg, 0.21 mmol), water (0.2 ml) and N,N-dimethylformamide (5 ml) was stirred at +65° C. for 24 hours. An additional batch of 2,3-dihydro-7-iodo-2-methyl-5-trifluoromethoxybenzofuran (0.7 g, 2.0 mmol) and palladium(II) acetate (22 mg, 0.1 mmol) was added and the reaction mixture was stirred at +65° C. for 48 hours. The mixture was cooled to room temperature, quenched with saturated aqueous NaHCO3 and extracted into diethyl ether. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 0-45%) to give the title compound (320 mg, 44%) as a 1:1 mixture of epimers.

Provenance & Evidence