Sodium Hydroxide → 1-(2-toluoylmethyl)-2-oxo-3-tert-butoxycarbonylamino-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979355Notes

Reaction equation

HRID 1979355 reaction equation
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:6]=2[N:5]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:4][CH:3]1[NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].Br[CH2:33][C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH3:42])=[O:35].[OH-].[Na+]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:37]1([CH3:42])[C:36]([C:34]([CH2:33][N:8]2[C:7]3[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:6]=3[N:5]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:4][CH:3]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:2]2=[O:1])=[O:35])=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 124306762-Bromo-2'-methylacetophenoneHCID 212018322-oxo-3-tert-butoxycarbonylamino-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212017461-(2-toluoylmethyl)-2-oxo-3-tert-butoxycarbonylamino-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 42.6%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

2-Oxo-3-tert-butoxycarbonylamino-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (23.1 g) was suspended in toluene (320 ml), 2-bromo-2′-methylacetophenone (13.9 g), 1N aqueous sodium hydroxide (160 ml) and tetra-n-butylammonium bromide (400 mg) were added thereto, the mixture was stirred for 2 hours at room temperature. After reaction, the reaction mixture was separated, the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=4:1), to thereby obtain 12.9 g of the titled compound.

Workup

  1. customAfter reaction
  2. customthe reaction mixture was separated
  3. washthe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-4cdaad52844a45fe929094de3696cd05
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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