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

HRID 417156Notes

Reaction equation

HRID 417156 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:19][CH2:18]3)[C:14](O)=[O:15])[C:11]3[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][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[CH2:19][CH2:18]3)[CH2:14][OH:15])[C:11]3[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66619353[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopropyl-acetic acid

Product 1

HCID 666194522-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-ethanolYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold suspension of 3.0 g (8.27 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopropyl-acetic acid in 105 ml tetrahydrofuran were added in portions 0.47 g (12.4 mmol) lithium aluminium hydride. After removal of the cooling bath the reaction mixture was stirred for 1 h at room temperature. The reaction mixture was poured onto 200 ml potassium sodium tartrate solution wan was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated to give a yellow solid which 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). The product containing fractions were pooled and evaporated until precipitation started. The suspension was filtered and washed with n-heptane to give the desired compound as an off-white solid (56%). MS (Turbo Spray): m/z=349.2 [M+H].

Workup

  1. customAfter removal of the cooling bath the reaction mixture
  2. additionThe reaction mixture was poured onto 200 ml potassium sodium tartrate solution wan
  3. extractionwas extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto give a yellow solid which
  9. customwas purified by silica gel chromatography
  10. washeluting with a gradient of heptane:ethyl acetate (100:0 to 50:50)
  11. additionThe product containing fractions
  12. customevaporated until precipitation
  13. filtrationThe suspension was filtered
  14. washwashed with n-heptane

Sources & evidence

ORD record
ord-a8d6105d8b954622930d5991405d95f8
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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