Ammonium Hydroxide → tert-butyl 2-(5-(methoxycarbonyl)-2,4-dimethylphenyl)-4,5,7,8-tetrahydroimidazo[4,5-d]azepine-6(1H)-carboxylate

HRID 1487960Notes

Reaction equation

HRID 1487960 reaction equation
[CH:1]([C:3]1[C:4]([CH3:14])=[CH:5][C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])=O.Br[CH:16]1[C:22](=O)[CH2:21][CH2:20][N:19]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:18][CH2:17]1.[OH-].[NH4+:32].C([O-])(=O)C.[NH4+:37]>CN(C)C=O.C(OCC)(=O)C>[CH3:11][O:10][C:8]([C:7]1[C:6]([CH3:13])=[CH:5][C:4]([CH3:14])=[C:3]([C:1]2[NH:37][C:16]3[CH2:17][CH2:18][N:19]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:21][C:22]=3[N:32]=2)[CH:12]=1)=[O:9]

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 517165Ammonium AcetateHCID 59143774Tert-butyl 4-bromo-5-oxoazepane-1-carboxylate2×HCID 90021893Methyl 5-formyl-2,4-dimethylbenzoate2×

Product 1

HCID 90066697tert-butyl 2-(5-(methoxycarbonyl)-2,4-dimethylphenyl)-4,5,7,8-tetrahydroimidazo[4,5-d]azepine-6(1H)-carboxylateYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

Into a 10-mL sealed tube, was placed methyl 5-formyl-2,4-dimethylbenzoate (compound 83.2, 500 mg, 2.60 mmol), tert-butyl 4-bromo-5-oxoazepane-1-carboxylate (compound 82.3, 1.1 g, 3.8 mmol), ammonium hydroxide (25%) (1.2 mL, 7.8 mmol), ammonium acetate (900 mg, 11.7 mmol) in N,N-dimethylformamide (6 mL). The resulting mixture was stirred for 3 h at 130° C. behind a blast shield, then cooled to room temperature and diluted with ethyl acetate (150 mL). The mixture was washed with brine (5×20 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with dichloromethane/methanol (10:1) as the eluent to yield 0.80 g (46%) of the title compound as yellow oil.

Workup

  1. customInto a 10-mL sealed tube
  2. temperaturecooled to room temperature
  3. washThe mixture was washed with brine (5×20 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography with dichloromethane/methanol (10:1) as the eluent

Sources & evidence

ORD record
ord-62e1b3ab25b143808a8fce4fee518ade
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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