benzyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate → benzyl 4-{4-[({2-[(tert-butoxycarbonyl)amino]phenyl}amino)carbonyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

Tetrakis(triphenylphosphine)palladium(0) (8.0 g, 6.92 mmol) was added to a stirred suspension of N-(2-t-butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2,-dioxaborolan-2-yl)benzamide (288 g, 657 mmol; prepared as described in International Patent Publication number WO 03/087057, Method 13, page 60) and benzyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (240 g, 657 mmol; prepared as described in Method 3 below) in 1,2-dimethoxyethane (3000 ml) and saturated aqueous sodium bicarbonate solution (3000 ml). The reaction mixture was heated to 80° C. for 7 h, before being allowed to cool to ambient temperature, with stirring. The reaction mixture was then poured onto water (2000 ml) and extracted with ethyl acetate. The organic extracts were then dried over magnesium sulfate, filtered and evaporated to dryness to give the crude product as a grey solid. This was purified by flash column chromatography on silica, eluting with ethyl acetate/hexane (30:70 v/v) to afford the title compound (279 g, 82%); NMR Spectrum: (DMSO-d6) δ 1.44 (s, 9H), 2.56 (m, 2H), 3.66 (m, 2H), 4.14 (m, 2H), 5.13 (s, 2H), 6.34 (m, 1H), 7.18 (m, 2H), 7.33 (m, 1H), 7.40 (m, 4H), 7.54 (m, 2H), 7.62 (d, 2H), 7.94 (d, 2H), 8.64 (br s, 1H), 9.81 (br s, 1H); Mass Spectrum: MNa+ 550.

Provenance & Evidence