Tetrahydrofuran → 5-Chloro-3-(4,4-difluorocyclohexylmethyl)-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acid

HRID 1468286Notes

Reaction equation

HRID 1468286 reaction equation
[Cl:1][C:2]1[N:7]2[C:8]([CH2:15][CH:16]3[CH2:21][CH2:20][C:19]([F:23])([F:22])[CH2:18][CH2:17]3)=[C:9]([C:11]([F:14])([F:13])[F:12])[N:10]=[C:6]2[CH:5]=[C:4]([C:24]([O:26]CC)=[O:25])[CH:3]=1.C1COCC1.[OH-].[Na+]>O>[Cl:1][C:2]1[N:7]2[C:8]([CH2:15][CH:16]3[CH2:21][CH2:20][C:19]([F:22])([F:23])[CH2:18][CH2:17]3)=[C:9]([C:11]([F:12])([F:13])[F:14])[N:10]=[C:6]2[CH:5]=[C:4]([C:24]([OH:26])=[O:25])[CH:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86710093Ethyl 5-chloro-3-{(4,4-difluorocyclohexyl)methyl}-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylate

Product 1

HCID 867100955-Chloro-3-(4,4-difluorocyclohexylmethyl)-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acidYield 113.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ethyl 5-chloro-3-(4,4-difluorocyclohexylmethyl)-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylate (62 mg, 0.146 mmol) obtained in step 2 was suspended in a mixed solvent of THF (2.0 mL) and water (2.0 mL), and the suspension was stirred under heat and reflux for 3 hours after adding sodium hydroxide (29 mg, 0.730 mmol). The reaction mixture was allowed to cool to room temperature, and the solvent was then evaporated under reduced pressure. The residue was extracted with water after adding chloroform. Following neutralization with 1 mol/L hydrochloric acid, the solvent was evaporated under reduced pressure. After adding a mixed solution of chloroform/methanol=4/1 to the residue, the insoluble matter was removed by filtration. The filtrate solvent was evaporated under reduced pressure to give a crude product of 5-chloro-3-(4,4-difluorocyclohexylmethyl)-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acid (66 mg).

Workup

  1. temperatureunder heat
  2. temperaturereflux for 3 hours
  3. customthe solvent was then evaporated under reduced pressure
  4. extractionThe residue was extracted with water
  5. additionafter adding chloroform
  6. customthe solvent was evaporated under reduced pressure
  7. additionAfter adding a mixed solution of chloroform/methanol=4/1 to the residue
  8. customthe insoluble matter was removed by filtration
  9. customThe filtrate solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-b719afdb62274606acfc2098d2f4018a
Source dataset
uspto-grants-2015_04
Patent number
US09000186B2

Reaction notes

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