Acetic Acid → tert-butyl (S)-4-((R)-1-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)-2,2-dimethylpropylamino)-1-methoxybutan-2-ylcarbamate

HRID 1028852Notes

Reaction equation

HRID 1028852 reaction equation
[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])[N:10]=[C:9]1[C@H:21]([NH2:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:27]([CH2:29][C@H:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:31][O:32][CH3:33])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])[N:10]=[C:9]1[C@H:21]([NH:26][CH2:27][CH2:29][C@H:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:31][O:32][CH3:33])[C:22]([CH3:23])([CH3:25])[CH3:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 57805652(R)-1-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)-2,2-dimethylpropan-1-amineHCID 57976564tert-butyl (S)-1-formyl-3-methoxypropan-2-ylcarbamate

Product 1

HCID 86602597tert-butyl (S)-4-((R)-1-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)-2,2-dimethylpropylamino)-1-methoxybutan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-1-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)-2,2-dimethylpropan-1-amine (1 eq) in dichloromethane was added tert-butyl (S)-1-formyl-3-methoxypropan-2-ylcarbamate (1.5 eq) and acetic acid (1 eq). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxy borohydride (2 eq) was added at 0° C. The reaction mixture was warmed to room temperature and stirred overnight. Solvent was concentrated and crude was partitioned between ethyl acetate and satd. sodium bicarbonate. The organic layer was washed with water, brine and dried over sodium sulfate. Purification by silica gel chromatography (25% EtOAc/Hexane) provide pure product as a white foamy solid.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred overnight
  3. concentrationSolvent was concentrated
  4. customcrude was partitioned between ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customPurification by silica gel chromatography (25% EtOAc/Hexane)
  8. customprovide pure product as a white foamy solid

Sources & evidence

ORD record
ord-b2e565d092e545fb9cf2a1d7c35034da
Source dataset
uspto-grants-2014_05
Patent number
US08735599B2

Reaction notes

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