Tetrahydrofuran → 3-(4,4-Difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylic acid

HRID 1468294Notes

Reaction equation

HRID 1468294 reaction equation
[F:1][C:2]1([F:28])[CH2:7][CH2:6][CH:5]([CH2:8][C:9]2[N:13]3[CH:14]=[C:15]([O:22][CH3:23])[C:16]([C:18]([O:20]C)=[O:19])=[CH:17][C:12]3=[N:11][C:10]=2[C:24]([F:27])([F:26])[F:25])[CH2:4][CH2:3]1.C1COCC1.[OH-].[Na+]>O>[F:28][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([CH2:8][C:9]2[N:13]3[CH:14]=[C:15]([O:22][CH3:23])[C:16]([C:18]([OH:20])=[O:19])=[CH:17][C:12]3=[N:11][C:10]=2[C:24]([F:25])([F:26])[F:27])[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86710108Methyl 3-(4,4-difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylate

Product 1

HCID 867101093-(4,4-Difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylic acidYield 99%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methyl 3-(4,4-difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylate (23 mg, 0.057 mmol) obtained in step 4 was suspended in a mixed solvent of THF (1.0 mL) and water (1.0 mL), and the suspension was stirred under heat and reflux for 3 hours after adding sodium hydroxide (11 mg, 0.283 mmol). The reaction mixture was allowed to cool to room temperature, and the solvent was evaporated under reduced pressure. The residue was extracted with water after adding chloroform, then neutralized 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 3-(4,4-difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylic acid (22.0 mg, yield 99%).

Workup

  1. temperatureunder heat
  2. temperaturereflux for 3 hours
  3. customthe solvent was 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-85b9a7cd0b624327983a367d575de834
Source dataset
uspto-grants-2015_04
Patent number
US09000186B2

Reaction notes

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