Lithium Chloride → (1R*,2R*,4'S*,5R*)-8-Benzyl-4'-(2-benzyloxy-5-trifluoromethoxyphenyl)-6-(tert-butoxycarbonyl)-2',3',4',5'-tetrahydro-1-phenylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]

Participants

Reaction Steps

A mixture of (1R*,2R*,5S*,6RS)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenylspiro[8-azabicyclo[3.2.1]octane-2,2′(5′H)-furan] (Description 27; 3.1 g, 7.17 mmol), 2-benzyloxy-5-trifluoromethoxyphenyl iodide (8.7 g, 22.1 mmol), tetra-n-butylammonium chloride (2.0 g, 6.2 mmol), lithium chloride (3.45 g, 77.5 mmol), potassium formate (2.8 g, 33 mmol), palladium(II) acetate (250 mg, 1.1 mmol), water (0.5 ml) and N,N-dimethylformamide (30 ml) was stirred at +70° C. for 20 hours. An additional batch of 2-benzyloxy-5-trifluoromethoxyphenyl iodide (3.6 g, 9.1 mmol) and palladium(II) acetate (130 mg, 0.56 mmol) was added and the reaction mixture was stirred at +70° C. for 24 hours. The mixture was cooled to room temperature, quenched with water and extracted into a 1:1 mixture of iso-hexane:diethyl ether (3×100 ml). 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 (3 g, 60%).

Provenance & Evidence