Water → 5-Fluoro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-2-(2,2,2-trifluoro-ethoxy)-benzonitrile

Temperature

5 °C

To a solution of 342 mg of trifluoroethanol in 2.1 mL of tetrahydrofuran at 5° C. was slowly added 4 mL of a molar solution of potassium tert-butoxide in tert-butanol. After stirring at 5° C. for 30 minutes, the resulting solution was slowly added to a solution of 1.25 g of 2,5-difluoro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile in 5.6 mL of tetrahydrofuran at −60° C. The resulting mixture was stirred overnight allowing the temperature to warm up to room temperature. It was then poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 70/ethyl acetate 30) to give 1.09 g of 5-fluoro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-2-(2,2,2-trifluoro-ethoxy)-benzonitrile.

1. customat 5° C.
2. stirringThe resulting mixture was stirred overnight
3. temperatureto warm up to room temperature
4. extractionextracted with dichloromethane
5. dry with materialThe organic extracts were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 70/ethyl acetate 30)

ORD record

ord-938484f94b5b4b2fbbc957371b82d391

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834030B2