Hydrochloric Acid → 1-(2-toluoylmethyl)-2-oxo-3-tert-butoxycarbonylamino-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979394Notes

Reaction equation

HRID 1979394 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]([CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])[CH2:4][CH:3]1[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].Br[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH3:37])=[O:30].[OH-].[Na+].Cl>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:32]1([CH3:37])[C:31]([C:29]([CH2:28][N:8]2[C:7]3[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:6]=3[N:5]([CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])[CH2:4][CH:3]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:2]2=[O:1])=[O:30])=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 124306762-Bromo-2'-methylacetophenoneHCID 212017442-oxo-3-tert-butoxycarbonylamino-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212016671-(2-toluoylmethyl)-2-oxo-3-tert-butoxycarbonylamino-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 59.3%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

2-Oxo-3-tert-butoxycarbonylamino-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (965 mg) was suspended in toluene (14 ml), 2-bromo-2′-methylacetophenone (686 mg), 1N aqueous sodium hydroxide (7 ml) and tetran-butylammonium bromide (20 mg) were added, and the mixture was stirred overnight at room temperature. The reaction mixture was weakly acidified with 1N hydrochloric acid, extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(chloroform:ethyl acetate=10:1), to thereby obtain 782 mg of the titled compound.

Workup

  1. extractionextracted with methylene chloride
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography(chloroform:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-0da8bf8cbca04f5fae723230506dd636
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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