2-Butenoic acid, 4-oxo-4-phenyl-, ethyl ester → 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, 100 ml of acetic acid are added and the solvent mixture is reacted at 20–30° C. for 18 h. After lactonization to compound (17), ammonium formate (51.4 g, 816 mmoles) and 10% Pd—C (26 g, 22 mmoles) are added. The reaction mixture is heated to 40° C. for 3 h, after that the catalyst is filtered off through Celite and solvents are evaporated off. The residue is taken up with acetone (600 ml) and acetic acid (200 ml), heated to dissolution and cooled. The resulting precipitate is filtered, washed with 80 ml of acetone1 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