Hydrochloric Acid → 8-[(2,6-Difluorobenzyl)oxy]-2-methyl-6-(morpholin-4-yl)imidazo[1,2-a]pyridine-3-carboxylic acid

HRID 1624089Notes

Reaction equation

HRID 1624089 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:18]([C:22]([O:24]CC)=[O:23])=[C:19]([CH3:21])[N:20]=2)[CH:9]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:11]=1.[OH-].[Li+].Cl>C1COCC1.CO>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:18]([C:22]([OH:24])=[O:23])=[C:19]([CH3:21])[N:20]=2)[CH:9]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86718169Ethyl 8-[(2,6-difluorobenzyl)oxy]-2-methyl-6-(morpholin-4-yl)imidazo[1,2-a]pyridine-3-carboxylate

Product 1

HCID 867181708-[(2,6-Difluorobenzyl)oxy]-2-methyl-6-(morpholin-4-yl)imidazo[1,2-a]pyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

400 mg of ethyl 8-[(2,6-difluorobenzyl)oxy]-2-methyl-6-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate (Example 34A; 0.927 mmol, 1 equivalent) were dissolved in 24 ml of THF/methanol 5:1, 4.6 ml of 1N aqueous lithium hydroxide solution (4.6 mmol, 5 equivalents) were added and the mixture was warmed to 40° C. and stirred at this temperature for 4 h. The mixture was cooled, acidified to pH 4 with 6 N hydrochloric acid and concentrated. Water was added to the residue and the mixture was extracted repeatedly with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried, filtered and concentrated. This gave 145 mg of the title compound (35% of theory) which was reacted further without further work-up.

Workup

  1. additionwere added
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated
  4. additionWater was added to the residue
  5. extractionthe mixture was extracted repeatedly with dichloromethane
  6. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThis gave 145 mg of the title compound (35% of theory) which was reacted further without further work-up

Sources & evidence

ORD record
ord-905233745eb242bca76e604bd0968d2c
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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