反应详情

To a solution of methyl 6-methyl-2-(3-methyl-1H-pyrazol-1-yl)nicotinate (3.7 g, 16 mmol) and trimethyl(trifluoromethyl)silane (11.4 g, 80.2 mmol) in toluene (60 ml), was added dropwise at −78° C. and then the solution of tetrabutyl ammonium fluoride (1.6 mL, 1.0 M in THF) was added dropwise to the reaction mixture at −78° C. After addition, the mixture was warmed slowly up to RT and stirred for 12 h. The reaction mixture was concentrated and the resulting residue was dissolved in methanol (30 mL). 6 N HCl (30 mL) was added to the reaction mixture and the resulting mixture was stirred for 2 h. The reaction mixture was concentrated, adjusted to pH 6 with sat.NaHCO3 and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo and purified by normal phase silica gel column (EtOAc/hepate) to provide 2,2,2-trifluoro-1-(6-methyl-2-(3-methyl-1H-pyrazol-1-yl)pyridin-3-yl)ethanone as a brown semi-solid.

1. additionAfter addition
2. concentrationThe reaction mixture was concentrated
3. dissolutionthe resulting residue was dissolved in methanol (30 mL)
4. addition6 N HCl (30 mL) was added to the reaction mixture
5. stirringthe resulting mixture was stirred for 2 h
6. concentrationThe reaction mixture was concentrated
7. extractionNaHCO3 and extracted with EtOAc
8. washThe combined organic layers were washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. custompurified by normal phase silica gel column (EtOAc/hepate)