Chloroacetone → Benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate

Participants

Reaction Steps

Add powdered potassium hydroxide (KOH) (0.72 g, 12.89 mmol) to a solution of benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate (2.0 g, 6.44 mmol), chloroacetone (1.19 g, 12.89 mmol), and tetrabutylammonium fluoride (1.29 mL, 1.29 mmol, 1M solution in THF) in tetrahydrofuran (65 mL). Stir the mixture for approximately 16 hours at ambient temperature. Add additional potassium hydroxide (0.361 g, 6.44 mmol), chloroacetone (0.59 g, 6.44 mmol), tetrabutylammonium fluoride (0.65 mL, 0.65 mmol, 1M solution in THF) and THF (20 mL) to the reaction and stir for approximately 48 hours at ambient temperature. Filter the reaction mixture through diatomaceous earth and concentrate the filtrate under reduced pressure. Purify the residue by flash chromatography (10% ethyl acetate/hexane to 100% ethyl acetate) to give the title compound (1.64 g, 65%): MS (m/z): 389 (M+23).

Provenance & Evidence