Hydrochloric Acid → 3-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acid

HRID 1951928Notes

Reaction equation

HRID 1951928 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([O:18]CC)=[O:17])[O:9][N:8]=1.O.[OH-].[Li+].Cl>CO.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([C:12]([F:14])([F:15])[F:13])=[C:10]([C:16]([OH:18])=[O:17])[O:9][N:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 66677499Ethyl 3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylate

Product 1

HCID 583741783-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acidYield 99%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylate (511 mg, 1.79 mmol) in methanol (12 mL) and water (3 mL) at room temperature was added lithium hydroxide, hydrate (74.9 mg, 1.79 mmol). The reaction mixture was stirred for 1 hr. A 1N aqueous solution of hydrochloric acid (1.8 mL) was added, and the solvent were removed under reduced pressure to afford 3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acid+1LiCl (531 mg, 1.767 mmol, 99% yield) as a white solid. The compound had an HPLC ret. time=0.725 min.—Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=258.8. 1H NMR (400 MHz, CD3OD) δ ppm 7.59 (dd, J=7.03, 5.02 Hz, 1H), 7.82 (d, J=7.78 Hz, 1H), 8.01 (td, J=7.78, 1.76 Hz, 1H), and 8.73 (d, 1H).

Workup

  1. customthe solvent were removed under reduced pressure

Sources & evidence

ORD record
ord-a8700d4f2ba54903b703de36d439dd23
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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