Aluminium lithium hydride → 2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-ethanol

HRID 417151Notes

Reaction equation

HRID 417151 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14](O)=[O:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21]3)[CH2:14][OH:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66619513[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopentyl-acetic acid

Product 1

HCID 666194742-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold solution of 2.0 g (5.12 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopentyl-acetic acid in 55 ml tetrahydrofuran were added in portions 0.29 g (7.64 mmol) lithium aluminium hydride. After removal of the cooling bath the reaction mixture was stirred for 2.5 h at room temperature and then poured onto 200 ml saturated aqueous tartrate solution. The phases were separated and the aqueous layer extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate (100:0 to 50:50). Yellow solid (68%). MS (Turbo Spray): m/z=377.2 [M+H].

Workup

  1. customAfter removal of the cooling bath the reaction mixture
  2. additionpoured onto 200 ml saturated aqueous tartrate solution
  3. customThe phases were separated
  4. extractionthe aqueous layer extracted three times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with a gradient of heptane:ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-32dac2a5d92b45d3823c90c426797747
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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