Ammonium Hydroxide → benzyl N-(2-methyl-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl)carbamate

HRID 2068541Notes

Reaction equation

HRID 2068541 reaction equation
[CH2:1]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C@@H:7]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:6]1=O)[C:2]([CH3:4])=O.C([O-])(=O)C.[NH4+:32].[OH-].[NH4+]>C(O)(=O)C>[NH3:5].[CH3:4][C:2]1[N:32]=[C:6]2[CH:7]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:5]2[CH:1]=1

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 517165Ammonium AcetateHCID 58304091Benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate

Product 2

HCID 222AmmoniaYield 10%HCID 58304090benzyl N-(2-methyl-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl)carbamateYield 63.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Combine benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate (0.7 g, 1.91 mmol) with ammonium acetate (2.94 g, 38.2 mmol) in acetic acid (20.0 mL) and heat at 115° C. for 24 hours, and then stir the mixture at ambient temperature for approximately 16 hours. Pour the reaction mixture into ice-water, basify it with ammonium hydroxide (28-30%), and extract with dichloromethane. Wash with water and brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (10% ethyl acetate/hexane to 50% ethyl acetate/hexane), then an SCX column (methanol, then 10% 2N ammonia in methanol/CH2Cl2) to give the title compound (0.21 g, 32%) as a white solid: MS (m/z): 348 (M+1). (Based on the final compounds made from this intermediate, the title compound is partially racemized.)

Workup

  1. extractionextract with dichloromethane
  2. washWash with water and brine
  3. dry with materialdry over sodium sulfate
  4. concentrationconcentrate the organic layer under reduced pressure
  5. customPurify the residue by flash chromatography (10% ethyl acetate/hexane to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b7240dbb2a704e9a878529f6f707fa05
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

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