Sodium Hydroxide → 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylic acid

HRID 1043944Notes

Reaction equation

HRID 1043944 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[C:12]([O:17][CH3:18])[C:11]=2[CH3:19])[CH:7]=[CH:6][C:5]=1[C:20]1[N:24]([C@H:25]2[CH2:29][CH2:28][O:27][CH2:26]2)[N:23]=[CH:22][C:21]=1[C:30]([O:32]CC)=[O:31]>C(O)C>[F:3][C:4]1[CH:9]=[C:8]([C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[C:12]([O:17][CH3:18])[C:11]=2[CH3:19])[CH:7]=[CH:6][C:5]=1[C:20]1[N:24]([C@H:25]2[CH2:29][CH2:28][O:27][CH2:26]2)[N:23]=[CH:22][C:21]=1[C:30]([OH:32])=[O:31]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86686373ethyl 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Product 1

HCID 866863755-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylic acidYield 96.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A 5 N aqueous sodium hydroxide solution (79 mL) was added to a solution of ethyl 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate (43.2 g) in ethanol (574 mL) at mom temperature, and the reaction mixture was stirred at 60° C. for two hours and 10 minutes. The reaction mixture was cooled to room temperature and then concentrated to half volume under reduced pressure. Water (300 mL) was added to the residue, and ethanol was distilled off under reduced pressure. MTBE (130 mL) was added to the resulting residue, and the aqueous layer was separated. The organic layer was extracted with water (30 mL). The combined aqueous layers were made acidic with 5 N hydrochloric acid (78 mL) under ice-cooling and extracted with ethyl acetate twice. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound (39.0 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated to half volume under reduced pressure
  3. additionWater (300 mL) was added to the residue, and ethanol
  4. distillationwas distilled off under reduced pressure
  5. additionMTBE (130 mL) was added to the resulting residue
  6. customthe aqueous layer was separated
  7. extractionThe organic layer was extracted with water (30 mL)
  8. temperaturecooling
  9. extractionextracted with ethyl acetate twice
  10. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1960ca39c2ff4bd1b5e07c6977276c69
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

Loading…