Hydrochloric Acid → (R/S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

HRID 77121Notes

Reaction equation

HRID 77121 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[C:23]([C:24]([F:27])([F:26])[F:25])=[C:22]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[O:21][N:20]=3)[O:16][N:15]=2)=[CH:10][CH:9]=1)[C:3]([O:5]CC)=[O:4].[Li+].[OH-].Cl>C1COCC1.CO>[OH:1][CH:2]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([C:19]3[C:23]([C:24]([F:25])([F:26])[F:27])=[C:22]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[O:21][N:20]=3)[O:16][N:15]=2)=[CH:10][CH:9]=1)[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 71263244HCID 71263244, compound

Product 1

HCID 67458660(R/S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acidYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R/S)-Ethyl 2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetate (Int-VIII, 380 mg, 0.83 mmol) was dissolved in THF (5.00 mL) and MeOH (5 mL). Then, 1N LiOH (0.83 mL, 0.83 mmol) was added. It was stirred for 20 min and additional 1N LiOH (0.83 mL, 0.83 mmol) was added. After stirring for 15 min, the solution was neutralized by 1N HCl to pH=5. The reaction mixture was concentrated and then EtOAc was added. The EtOAc was washed with brine. The organic layer was dried, filtered and concentrated to give (R/S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-IX, 376 mg, 0.785 mmol, 95% yield): LCMS=432.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.02-8.20 (2 H, m), 7.49-7.79 (7 H, m), 5.27 (1 H, s).

Workup

  1. stirringAfter stirring for 15 min
  2. concentrationThe reaction mixture was concentrated
  3. additionEtOAc was added
  4. washThe EtOAc was washed with brine
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-931ea511bcbb4b79a3155f5893af9fb7
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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