Bromide ion → 3-[[1-[[2'-Cyano-[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]amino]-1,1-dimethyl-3-oxopropylcarbamic acid, 1,1-dimethylethyl ester

Participants

Reaction Steps

To a solution of 0.83 g (2.21 mmol) of 3-t-butoxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide (Example 57, Step A) in 6 mL of dry dimethylformamide at room temperature under nitrogen was added 97 mg of 60% sodium hydride dispersion in oil (58 mg NaH, 2.43 mmol, 1.1 eq). After stirring for 1 hour, a solution of 780 mg (2.88 mmol, 1.3 eq) of 4'-bromomethyl-1,1'-biphenyl-2-nitrile (Step C) in 2.0 mL of dimethylformamide was added via cannula. The flask which originally contained the bromide was washed with 1 mL of dry dimethylformamide which was then added to the reaction mixture via cannula. After stirring at room temperature for 3 hours, the reaction was diluted with 200 mL of ethyl acetate, washed with 50 mL of water and 50 mL of brine. The organic layer was separated, dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash chromatography on silica gel, eluting with ethyl acetate/hexane (6:4), to afford 1.13 g (90%) of the product as a white foam. 1H NMR (200 MHz,CDCl3): 1.32 (s,3H), 1.40 (s,12H), 1.85 (m,1H), 2.35-2.70 (m,5H), 4.52 (m,1H), 4.90 (d,12 Hz,1H), 5.21 (d,12 Hz,1H), 6.70 (d,5 Hz,1H), 7.10-7.65 (m,12H), 7.72 (d,6 Hz,1H). FAB-MS: calculated for C34H38N4O4 566; found 567 (M+H).

Provenance & Evidence