Potassium Iodide → (+/-)-1-tert-butylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahy dro-2H-1,5-benzodiazepine

HRID 1698767Notes

Reaction equation

HRID 1698767 reaction equation
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:4][CH:3]1[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].[C:27]([C:31]([CH2:33]Br)=[O:32])([CH3:30])([CH3:29])[CH3:28].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CS(C)=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:27]([C:31]([CH2:33][N:8]1[C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:4][CH:3]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:2]1=[O:1])=[O:32])([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 21642BromopinacoloneHCID 154908332-Oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 15490834(+/-)-1-tert-butylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahy dro-2H-1,5-benzodiazepine

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (±)-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (3.35 g) in dimethyl sulfoxide (30 mL), bromomethyl tert-butyl ketone (2 g), potassium carbonate (1.55 g), potassium iodide (125mg) and tetra (n-butyl) ammonium bromide (120mg) were added, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over an hydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel colomn chromatography (ethyl acetate: n-hexane=1:3), whereby the title compound (2.3 g) was obtained.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over an hydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel colomn chromatography (ethyl acetate: n-hexane=1:3), whereby the title compound (2.3 g)
  6. customwas obtained

Sources & evidence

ORD record
ord-4b32c43ddf464b20b911d87f369ae02a
Source dataset
uspto-grants-2002_02
Patent number
US06344452B1

Reaction notes

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