Bromopinacolone → 1-tert-butylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979365Notes

Reaction equation

HRID 1979365 reaction equation
[H-].[Na+].[O:3]=[C:4]1[NH:10][C:9]2[CH:11]=[C:12]([CH3:15])[CH:13]=[CH:14][C:8]=2[N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:6][CH:5]1[NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].Br[CH2:31][C:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33]>CN(C)C=O>[C:34]([C:32]([CH2:31][N:10]1[C:9]2[CH:11]=[C:12]([CH3:15])[CH:13]=[CH:14][C:8]=2[N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:6][CH:5]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:4]1=[O:3])=[O:33])([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 21642BromopinacoloneHCID 24758Sodium hydrideHCID 212017702-oxo-3-tert-butoxycarbonylamino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212020161-tert-butylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 55.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

60% Sodium hydride (33 mg) was suspended in anhydrous N,N-dimethylformamide (10 ml), under ice-cooling 2-oxo-3-tert-butoxycarbonylamino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (200 mg) obtained from Referentioal Example 5, and the mixture was stirred for one hour at room temperature. Subsequently, bromomethyl-tert-butylketone (147 mg) was added, stirred for one hour at room temperature. Ice-water was added to the reaction mixture, extracted with ethyl acetate, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, diisopropyl ether was added to the residue for crystallization, crystals so precipitated were collected by filtration, to thereby obtain 140 mg of the titled compound.

Workup

  1. stirringstirred for one hour at room temperature
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure, diisopropyl ether
  6. additionwas added to the residue for crystallization, crystals
  7. customso precipitated
  8. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-06aabe20e21a4008b4094427f757baf2
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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