Hydrochloric Acid → [2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid methyl ester

HRID 417120Notes

Reaction equation

HRID 417120 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14]([OH:16])=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:31]I.Cl>CN(C)C=O.C(OCC)(=O)C>[CH3:31][O:15][C:14](=[O:16])[CH:13]([N:12]1[C:11]2[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=2[N:9]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66619321[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid

Product 1

HCID 66619263[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 1 g (2.47 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid in 10 ml N,N-dimethylformamide, 129 mg (2.964 mmol) sodium hydride (55% dispersion in mineral oil) and 368 mg (2.594 mmol) methyl iodide were added. The reaction was stirred at room temperature for 2 h and then poured on 100 ml ethyl acetate and 100 ml 1M aqueous hydrochloric acid. The phases were separated and the organic layer washed two times with 100 ml water and 100 ml brine. The combined water layers were extracted with 100 ml ethyl acetate, 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 n-heptane:ethyl acetate (100:0 to 60:40). Colorless solid (92%). MS (Turbo Spray): m/z=419.1 [M+H].

Workup

  1. customThe phases were separated
  2. washthe organic layer washed two times with 100 ml water and 100 ml brine
  3. extractionThe combined water layers were extracted with 100 ml ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 60:40)

Sources & evidence

ORD record
ord-930688115bea4252bf2641009b918d8a
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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