Methanol → (R/S)-2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

HRID 77120Notes

Reaction equation

HRID 77120 reaction equation
[OH:1][CH:2]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([C:19]3[CH:20]=[N:21][N:22]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:23]=3[C:24]([F:27])([F:26])[F:25])[O:16][N:15]=2)=[CH:10][CH:9]=1)[C:3]([O:5]CC)=[O:4].CO.[Li+].[OH-]>C1COCC1>[OH:1][CH:2]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([C:19]3[CH:20]=[N:21][N:22]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:23]=3[C:24]([F:25])([F:26])[F:27])[O:16][N:15]=2)=[CH:10][CH:9]=1)[C:3]([OH:5])=[O:4]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium Hydroxide3×HCID 68232671(R/S)-Ethyl 2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetate

Product 1

HCID 67460691(R/S)-2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acidYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R/S)-Ethyl 2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetate (Int-VI, 1.95 g, 4.25 mmol) was dissolved in THF (11 mL) and MeOH (5.50 mL) was added. Then, 1N LiOH (4.25 mL, 4.25 mmol) was added. It was stirred for 10 min and additional 1N LiOH (0.85 mL, 0.85 mmol) was added. After 10 min, more 1N LiOH (0.42 mL, 0.42 mmol) was added. After stirring for 10 min, the solution was concentrated and then EtOAc was added. The EtOAc was washed with 1 N HCl aqueous. The organic layer was dried (MgSO4), filtered and concentrated to give (R/S)-2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-VII, 1.8 g, 4.1 mmol, 97%): LCMS=431.1 [M+H]+.

Workup

  1. waitAfter 10 min
  2. stirringAfter stirring for 10 min
  3. concentrationthe solution was concentrated
  4. additionEtOAc was added
  5. washThe EtOAc was washed with 1 N HCl aqueous
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-773ce2da25e94d48bddbfac53ab56570
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

Loading…