Sodium Hydroxide → 5-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazole-3-carboxylic acid

A solution of ethyl 5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-3-carboxylate (138 mg, 0.482 mmol) and 1N aqueous sodium hydroxide (579 μL, 0.579 mmol) in ethanol (4.5 mL) was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water (0.5 mL) and acidified with a 1N aqueous solution of hydrochloric acid to a pH of ˜3.0. The solution was extracted with ethyl acetate (3×2 mL). The organic layer was washed with water (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded 5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-3-carboxylic acid (0.093, 0.361 mmol, 75% yield). The product had an HPLC retention. time=1.57 min.—Column: YMC S5 COMBISCREEN® 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=259.0. 1H NMR (400 MHz, CD3OD) δ ppm 7.60-7.65 (m, 2H), 7.92 (d, J=8.03 Hz, 2H), 8.02-8.09 (m, 2H), and 8.78 (d, 2H).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionthe residue was diluted with water (0.5 mL)
3. extractionThe solution was extracted with ethyl acetate (3×2 mL)
4. washThe organic layer was washed with water (1 mL)
5. washwashed with brine (1 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationConcentration under reduced pressure

ORD record

ord-b40f40f3aca0416f8fbc3a78ae7e8408

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404672B2