Acetic Acid → 3-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one

Participants

Reaction Conditions

Reaction Steps

Ethyl 3-benzoylacrylate (13a) (55.6 g, 272 mmoles) is dropped into a solution of (3S)-3-amino-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (11) (66.2 g, 228 mmoles) in 200 ml of toluene, at room temperature in 1 h. The resulting mixture is left under stirring for 18 h, then added with 10% Pd—C (26 g, 22 mmoles) and hydrogenated at 3 atm for 18 h at room temperature. After completion of the reaction the catalyst is filtered off through Celite, 50 ml of acetic acid are added and the solvent mixture is evaporated to kettle temperature of 110–120° C. The residue is taken up in 200 ml of toluene, 50 ml of acetic acid then cyclohexene (50 ml) and 10% Pd—C (26 g, 22 mmoles) are added. The reaction mixture is heated to 80° C. for 18 h, after that the catalyst is filtered off through Celite and solvents are evaporated off. The residue is taken up with isopropanol (500 ml) and the resulting precipitate is filtered, washed with 20 ml of isopropanol and dried to give 3-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (15) (60.7 g, yield: 54%).

Provenance & Evidence