Sodium Hydroxide → 1-{[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid

HRID 623926Notes

Reaction equation

HRID 623926 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C:27]2[C:28]([CH3:44])=[CH:29][C:30]([O:33][CH2:34][C:35]3([C:39]([O:41]CC)=[O:40])[CH2:38][CH2:37][CH2:36]3)=[N:31][CH:32]=2)[CH:7]=[CH:8][C:9]=1[C:10]1[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[N:14]=1>CO>[Cl:3][C:4]1[CH:5]=[C:6]([C:27]2[C:28]([CH3:44])=[CH:29][C:30]([O:33][CH2:34][C:35]3([C:39]([OH:41])=[O:40])[CH2:36][CH2:37][CH2:38]3)=[N:31][CH:32]=2)[CH:7]=[CH:8][C:9]=1[C:10]1[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:12]=[C:13]([C:15]([F:18])([F:16])[F:17])[N:14]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86698182ethyl 1-{[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylate

Product 1

HCID 866981831-{[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acidYield 100.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methanol (4.3 mL) and 1N aqueous sodium hydroxide solution (1.7 mL) were added to ethyl 1-{[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylate (213 mg), and the mixture was refluxed for 1 hour. Methanol was distilled off under reduced pressure, and the residue was neutralized by 1N hydrochloric acid. The mixture was extracted with ethyl acetate, the organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate. After concentrating the mixture under reduced pressure, the obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:0 to 95:5) to obtain 1-{[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid (205 mg).

Workup

  1. temperaturethe mixture was refluxed for 1 hour
  2. distillationMethanol was distilled off under reduced pressure
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with a saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationAfter concentrating the mixture under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:0 to 95:5)

Sources & evidence

ORD record
ord-a1d2d3088d2449b0ad22a4da2b3d19d7
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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