反应详情

Combine methanol (5000 mL) and 5N aqueous hydrogen chloride solution (1393 mL, 5.57 mol) and heat to 35° C. for 15 minutes. Add tert-butyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate (Armstrong III, Joseph D, et al, Tetrahedron Let. 35(20) pp. 3239-3242 (1994) (770 g, mmol and commercially available) portionwise over 1 hour. Concentrate the mixture under reduced pressure to a white solid. Combine this solid with additional (3R)-3-amino-1,3,4,5-tetrahydro-1-benzazepin-2-one (different lot, same method; 660 g, 3.78 mol) and dissolve in water (2.5 L). To the resulting solution add sodium carbonate (3.17 kg, 3.18 mol) and acetonitrile (7.5 L). Add benzyl chloroformate (7.14 mol, 1.21 Kg) dropwise over 2 hours. After 2 hours at ambient temperature, add ethyl acetate (8 L) and filter. Wash the wet cake with water (4.0 L), acetonitrile (2.0 L), and ethyl acetate (3.0 L). Dry the solid under reduced pressure for 48 hours to give the title compound (2.14 kg, 105%): MS (m/z): 310.8 (M+1).

1. concentrationConcentrate the mixture under reduced pressure to a white solid
2. waitAfter 2 hours at ambient temperature
3. filtrationfilter
4. washWash the wet cake with water (4.0 L), acetonitrile (2.0 L), and ethyl acetate (3.0 L)
5. customDry the solid under reduced pressure for 48 hours