Potassium Iodide → 1-cyclohexylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979472Notes

Reaction equation

HRID 1979472 reaction equation
Br[CH2:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[O:19]=[C:20]1[NH:26][C:25]2[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=2[N:23]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH2:22][CH:21]1[NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CS(C)=O>[CH:5]1([C:3]([CH2:2][N:26]2[C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[N:23]([CH:31]3[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)[CH2:22][CH:21]([NH:37][C:38]([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[O:39])[C:20]2=[O:19])=[O:4])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 111600272-Bromo-1-cyclohexylethanoneHCID 154908332-Oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212016381-cyclohexylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 37.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Bromomethylcyclohexylketone (861 mg), potassium iodide (23 mg), tetra n-butylammonium bromide (27 mg) and potassium carbonate (464 mg) were added to a solution of 2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (1 g) in dimethylsulfoxide (10 ml), the mixture was stirred overnight at room temperature. Ice-water was added to the reaction mixture, extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(ethyl acetate:n-hexane=1:5) and subsequently purified by silica gel column chromatography(silica gel NH-DM1020, produced by Fujisilicia Co. Ltd., ethyl acetate:n-hexane=1:5), to thereby obtain 500 mg of the title compound.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  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(ethyl acetate:n-hexane=1:5)
  6. customsubsequently purified by silica gel column chromatography(silica gel NH-DM1020, produced by Fujisilicia Co. Ltd., ethyl acetate:n-hexane=1:5)

Sources & evidence

ORD record
ord-8852a22f64de4bbe813aa21444045b0b
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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