Sodium cyanoborohydride → 3-[[2,2-Dimethyl-1,3-dioxolan-4(S)-yl]methyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide

Participants

Reaction Steps

To a solution of 368 mg (1.34 mmol) of 3-amino-3-methyl- N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide (Step A) in 10 mL of dry methanol was added 1.5 g of dry 4 Å powdered molecular sieves followed by a solution of 520 mg (4.0 mmol) of D-glyceraldehyde acetonide (used crude as prepared according to the procedure of L. W. Hertel, C. S. Grossman and J. S. Kroin, Syn. Comm. 1991, 21, 151-154.) in 5 mL of dry methanol. The pH of the mixture was carefully adjusted to 6 by the addition of 3 drops of acetic acid. The reaction was stirred for 5 hours at room temperature at which time 4.0 mL (4.0 mmol) of a 1.0 M solution of sodium cyanoborohydride in tetrahydrofuran was added by syringe. The reaction was stirred for 16 hours then filtered through a pad of Celite. The solvent was removed under vacuum to afford a clear oil which was purified by flash column chromatography on silica gel eluting with chloroformB 10% aqueous ammonium hydroxide (33%) in methanol (92:8) to afford 387 mg (78%) of the product as a white solid. 1H NMR (200 MHz, CD3OD): δ 1.10 (s, 6H), 1.28 (s, 3H), 1.34 (s, 3H), 2.08 (m, 1H), 2.26 (dd; 16, 15 Hz; 2H), 2.44 (m, 1H), 2.58-2.75 (m, 3H), 2.87 (m, 1H), 3.63 (dd; 8, 7 Hz; 1H), 4.05 (dd; 8, 7 Hz; 1H), 4.20 (m, 1H), 4.38 (dd; 12, 8 Hz; 1H), 4.84 (s, 1H), 7.00-7.40 (m, 4H). FAB-MS: calculated for C21H31N3O4 389; found 390 (M+H, 100%).

Provenance & Evidence