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

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Reaction Steps

Ethyl 3-benzoylacrylate (13a) (55.6 g, 272 mmoles) is drooped 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 a solution of sodium borohydride (228 mmoles 8.6 g) and tetrabutylammonium chloride (5.0 g) in 50 ml of 0.1 M NaOH is added and the mixture is stirred at room temperature for 18 h. The aqueous phase is separated, 50 ml of acetic acid are added to the organic phase and the mixture is left under stirring for 30′, then added with 10% Pd—C (26 g, 22 mmoles) and ammonium formate (456 mmoles, 33.3 g) and left under stirring for 4 h. Afterwards, the catalyst is filtered off through Celite and 100 ml of water is added. 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) (53.9 g, yield: 48%).

Provenance & Evidence