Lithium Chloride → HCID 11307776, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-benzyloxy-5-(trifluoromethoxy)iodobenzene (Description 22b, 21.8 g, 55.2 mmol), (5R,6S)-7-(tert-butoxycarbonyl)-6-phenyl-7-aza-1-oxa-spiro[4.5]dec-3-ene (Description 21, 7.0 g, 22.1 mmol), tetra-n-butylammonium chloride (6.18 g, 22.2 mmol), lithium chloride (9.35 g, 0.22 mol) and potassium formate (5.64 g, 67.0 mmol) in dimethylformamide (100 ml) was degassed with a firestone valve (x5) and purged with nitrogen. Palladium acetate (491 mg, 2.2 mmol) was added and the mixture was degassed with a firestone valve (x5). The mixture was stirred at 60° C. for 15 hours, then further 2-benzyloxy-5-(trifluoromethoxy)iodobenzene (Description 22b, 4.32 g, 11.0 mmol), potassium formate (2.78 g, 33.5 mmol) and palladium acetate 260 mg, 1.1 mmol) were added. The mixture was stirred at 60° C. for 22 hours, cooled and filtered. The solvent was evaporated under reduced pressure, water (600 ml) was added and the mixture was extracted with ethyl acetate (2×300 ml). The combined organic fractions were washed with brine (300 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/CH2Cl2 (75:25 increasing to 0:100) then CH2Cl2 /EtOAc (95:5), to give the title compound (9.42 g, 73%). 1H NMR (360 MHz, CDCl3) δ 7.56 (2H, d, J 7.7 Hz), 7.40-7.20 (8H, m), 7.14 (1H, d, J 2.0 Hz), 7.00 (1H, dd, J 8.9, 2.0 Hz), 6.88 (1H, d, J 8.9 Hz), 5.30 (1H, s), 5.08 (2H, s), 4.27 (1H, m), 3.97 (1H, m), 3.87 (2H, m), 2.78 (1H, m), 2.56 (1H, m), 2.15 (1H, m), 1.96 (1H, m), 1.67 (3H, m), and 1.42 (9H, s).

Provenance & Evidence