Ammonium Hydroxide → t-Butyl 2-(2-cyclobutyl-5-(methoxycarbonyl)-4-methylphenyl)-4,5,7,8-tetrahydroimidazo[4,5-d]azepine-6(1H)-carboxylate

HRID 1487954Notes

Reaction equation

HRID 1487954 reaction equation
[CH:1]1([C:5]2[C:14]([CH:15]=O)=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([CH3:17])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.C([O-])(=O)C.[NH4+:22].Br[CH:24]1[C:30](=O)[CH2:29][CH2:28][N:27]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:26][CH2:25]1.[OH-].[NH4+:40]>CN(C)C=O>[CH:1]1([C:5]2[CH:6]=[C:7]([CH3:17])[C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:13][C:14]=2[C:15]2[NH:40][C:24]3[CH2:25][CH2:26][N:27]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:29][C:30]=3[N:22]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 517165Ammonium AcetateHCID 59143774Tert-butyl 4-bromo-5-oxoazepane-1-carboxylate2×HCID 90021669Methyl 4-cyclobutyl-5-formyl-2-methylbenzoate2×

Product 1

HCID 90066675t-Butyl 2-(2-cyclobutyl-5-(methoxycarbonyl)-4-methylphenyl)-4,5,7,8-tetrahydroimidazo[4,5-d]azepine-6(1H)-carboxylateYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

Into a 100-mL round-bottom flask, was placed a mixture of methyl 4-cyclobutyl-5-formyl-2-methylbenzoate (compound 82.5, 300 mg, 1.29 mmol), ammonium acetate (449 mg, 5.83 mmol), tert-butyl 4-bromo-5-oxoazepane-1-carboxylate (compound 82.3, 564 mg, 1.93 mmol) and ammonium hydroxide (25%) (597 μL, 3.87 mmol) in N,N-dimethylformamide (8 mL). The resulting mixture was stirred for 4 h at 130° C., then cooled and quenched with water/ice (10 mL). The aqueous phase was extracted with ethyl acetate (2×30 mL) and the combined organic layers were washed with brine (3×10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/1) as the eluent to yield 0.10 g (18%) of the title compound as a white solid.

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. temperaturecooled
  3. customquenched with water/ice (10 mL)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×30 mL)
  5. washthe combined organic layers were washed with brine (3×10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/1) as the eluent

Sources & evidence

ORD record
ord-b9269cc6b448461db096919c9a053ee4
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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