Potassium Carbonate → (R)-(-)-1-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)urea

HRID 1979467Notes

Reaction equation

HRID 1979467 reaction equation
Br[CH2:2][C:3]([C:5]([CH3:8])([CH3:7])[CH3:6])=[O:4].C(=O)([O-])[O-].[K+].[K+].[O:15]=[C:16]1[NH:22][C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[N:19]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:18][C@H:17]1[NH:33][C:34]([NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH:38]=1)=[O:35]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CS(C)=O.[I-].[K+]>[C:5]([C:3]([CH2:2][N:22]1[C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[N:19]([CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:18][C@@H:17]([NH:33][C:34]([NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])[CH:38]=2)=[O:35])[C:16]1=[O:15])=[O:4])([CH3:8])([CH3:7])[CH3:6]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 21642BromopinacoloneHCID 54084555(R)-(-)-1-(2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)urea

Product 1

HCID 53986084(R)-(-)-1-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)ureaYield 95%

Reagents, catalysts & solvents 3

HCID 4875Potassium IodideCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Bromomethyl tert-butylketone (2.95 g), potassium iodide (125 mg), tetra n-butylammonium bromide (145 mg) and potassium carbonate (2.07 g) were added to a solution of (R)-(−)-1-(2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)urea (7.18 g) in dimethylsulfoxide (100ml), the mixture was stirred for 2hours at room temperature. The reaction mixture was poured into ice-water, extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(ethyl acetate:n-hexane=1:2), to thereby obtain 8.22 g of the titled compound (Yield 95%).

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=1:2)

Sources & evidence

ORD record
ord-2e787b1846044463b4064a03af12920b
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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