Sodium borohydride → alpha-[1-[4-[4-(1,1-dimethylethyl)phenyl]-4-hydroxybutyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole-2-methanol

HRID 1647050Notes

Reaction equation

HRID 1647050 reaction equation
[CH3:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:40])[CH2:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([C:21]([C:23]3[N:27]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[C:26]4[CH:36]=[CH:37][CH:38]=[CH:39][C:25]=4[N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[CH:7][CH:6]=1)([CH3:4])[CH3:3].[BH4-].[Na+]>CO>[CH3:4][C:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([OH:40])[CH2:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([CH:21]([C:23]3[N:27]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[C:26]4[CH:36]=[CH:37][CH:38]=[CH:39][C:25]=4[N:24]=3)[OH:22])[CH2:17][CH2:16]2)=[CH:7][CH:6]=1)([CH3:1])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 198004991-[4-(1,1-dimethylethyl)phenyl]-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbonyl]-1-piperidinyl]-1-butanone

Product 1

HCID 19800498alpha-[1-[4-[4-(1,1-dimethylethyl)phenyl]-4-hydroxybutyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole-2-methanol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred, room temperature, solution of 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbonyl]-1-piperidinyl]-1-butanone (2.1 g, 3.9×10-3 mole) and methanol (80 ml) was added NaBH4 (0.42 g, 1.1×10-2 mole). After stirring overnight, the methanol was evaporated at reduced pressure. The concentrate was dissolved in a two phase mixture of EtOAc/H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc. The EtOAc extracts were combined, washed with saturated aqueous NaCl, and dried over anhydrous MgSO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure leaving a solid. Crystallization from cyclohexane/hexane afforded α-[1-[4-[4-(1,1-dimethylethyl)phenyl]-4-hydroxybutyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole-2-methanol as a colorless solid: 1.6 g (75%), m.p. 87-90° C.

Workup

  1. customthe methanol was evaporated at reduced pressure
  2. dissolutionThe concentrate was dissolved in a two phase mixture of EtOAc/H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc
  5. washwashed with saturated aqueous NaCl
  6. dry with materialdried over anhydrous MgSO4
  7. customThe drying agent was removed by filtration
  8. customthe filtrate was evaporated at reduced pressure
  9. customleaving a solid
  10. customCrystallization from cyclohexane/hexane

Sources & evidence

ORD record
ord-40036925f5324227b2af33aed2cc564b
Source dataset
uspto-grants-1993_01
Patent number
US05182399

Reaction notes

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