Hydrochloric Acid → Benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate

HRID 2068528노트

반응식

HRID 2068528 반응식
Cl.[O:2]=[C:3]1[C@H:9]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])(C)C)[CH2:8][CH2:7][C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[NH:4]1.N[C@@H]1C[CH2:28][C:27]2C=C[CH:32]=[CH:33][C:26]=2NC1=O.C(=O)([O-])[O-].[Na+].[Na+].ClC(OCC1C=CC=CC=1)=O>O.C(OCC)(=O)C.C(#N)C.CO>[O:2]=[C:3]1[C@H:9]([NH:10][C:11](=[O:17])[O:12][CH2:13][C:16]2[CH:32]=[CH:33][CH:26]=[CH:27][CH:28]=2)[CH2:8][CH2:7][C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[NH:4]1

참가 물질

10

반응물 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 10103689(R)-3-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-oneHCID 10923829(R)-(2-Oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)-carbamic acid tert-butyl ester

생성물 1

HCID 58304068Benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate수율 105%

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-285664f0717846739a2f66066f24dc97
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299061B2

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