Sodium Carbonate → (RS)-4-(3'-difluoromethoxy-biphenyl-3-yl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine

Participants

Reaction Conditions

Reaction Steps

A dried pressure tube was charged with (RS)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine (Building Block S) (131 mg, 0.3 mmol), 3-(difluoromethoxy)-benzeneboronic acid (93 mg, 0.5 mmol), triphenylphosphine (18 mg, 0.1 mmol), 2 N sodium carbonate solution (0.5 mL), and 1,2-dimethoxyethane (3 mL). The mixture was purged with nitrogen before palladium(II) acetate (7 mg, 0.03 mmol) was added. The sealed pressure tube was heated at 100° C. for 15 hours. For the working-up, the reaction mixture was cooled and evaporated under reduced pressure. The residue was directly chromatographed on silica gel using a gradient of dichloromethane/methanol=100/0 to 95/5 as the eluent. There were obtained 43 mg (28% of theory) of (RS)-4-(3′-difluoromethoxy-biphenyl-3-yl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine as light yellow solid. Mass (calculated) C24H20F4N2O3 [460]; (found) [M+H]+=461.

Provenance & Evidence