反应详情

A solution of 3-amino-1-carboxymethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (10.0 g) and ethyl benzylpyruvate (26.4 g) in acetic acid (75 ml) and methanol (75 ml) was stirred at room temperature under nitrogen for 1 hour. Sodium cyanoborohydride (3.4 g) in methanol (25 ml) was added dropwise over 4 hours. The reaction mixture was stirred at room temperature for 24 hours. Concentrated hydrochloric acid (4 ml) was added dropwise, and the mixture stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness. The residue was partitioned between 150 ml of water and 50 ml of ether and adjusted to pH 9 with 40% sodium hydroxide. The layers were separated and the ether layer was discarded. The aqueous layer was adjusted to pH 4.3 with concentrated hydrochloric acid and extracted with 3×75 ml of ethyl acetate. The organic portions were dried (magnesium sulfate) and concentrated to dryness. Hydrogen chloride gas was bubbled into a solution of the crude product in 310 ml of methylene chloride for 5 minutes. The solution was evaporated and the residue was stirred in 225 ml of ether. The product was collected by filtration to give a 70:30 diastereomeric mixture as determined by high pressure liquid chromatography. The product was recrystallized from ethanol/ethyl acetate (1:3) to give 1-carboxymethyl-3-(1-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one hydrochloride melting at 246°-248° (dec.) and corresponding to the racemic isomer B.

1. stirringthe mixture stirred at room temperature for 1 hour
2. customThe reaction mixture was evaporated to dryness
3. customThe residue was partitioned between 150 ml of water and 50 ml of ether
4. customThe layers were separated
5. extractionextracted with 3×75 ml of ethyl acetate
6. dry with materialThe organic portions were dried (magnesium sulfate)
7. concentrationconcentrated to dryness
8. customHydrogen chloride gas was bubbled into a solution of the crude product in 310 ml of methylene chloride for 5 minutes
9. customThe solution was evaporated
10. stirringthe residue was stirred in 225 ml of ether
11. filtrationThe product was collected by filtration
12. customto give a 70:30 diastereomeric mixture
13. customThe product was recrystallized from ethanol/ethyl acetate (1:3)