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

HRID 2068528Notes

Reaction equation

HRID 2068528 reaction equation
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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-285664f0717846739a2f66066f24dc97
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

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