Acetonitrile → 1-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
Reaktionsgleichung
Br[CH:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[N:4]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:3]1=[O:19].N[C@H:21]1[CH2:28][CH2:27][CH2:26][NH:25][C:23](=[O:24])[CH2:22]1.C(#[N:31])C>>[CH2:17]([O:16][C:14]([CH2:13][N:4]1[C:5]2[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=2[CH2:7][CH2:8][CH:2]([NH:31][C@H:22]2[CH2:21][CH2:28][CH2:27][CH2:26][NH:25][C:23]2=[O:24])[C:3]1=[O:19])=[O:15])[CH3:18]Komponenten
4
Versuchsvorschrift
A solution of 15.3 g of 3-bromo-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one and 30 g of 3-(S)-amino-ε-caprolactam [L-(-)-3-aminocaprolactam] in 400 ml of acetonitrile is heated under reflux for 48 hours. The reaction mixture is cooled to room temperature, filtered, and the filtrate is evaporated to dryness. The residue is dissolved in 200 ml methylene chloride, the methylene chloride solution is washed with 2×200 ml of water and then extracted with 2×100 ml of 2N hydrochloric acid. The acidic extract is neutralized to pH 8 by addition of solid potassium carbonate. Extraction with methylene chloride yields 1-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one as a mixture of diastereoisomers. The crude product is recrystallized from methanol to yield 1-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-(3S)-benzazepin-2-one, m.p. 148°- 150°, the compound of formula IIa wherein COR represents carboxy.