Reacción #89308

Ecuación de reacción

2-Chloro-5-(trifluoromethyl)pyridine

((2S,3R)-2-(hydroxymethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

NaH

→

title compound

((2S,3R)-3-Methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)oxy)methyl)piperidin-1-yl) (5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe solution was warmed
2. 2
   Temperaturato reflux for 2 h
3. 3
   TemperaturaThe reaction was cooled
4. 4
   Otroquenched with satd
5. 5
   Concentraciónaq. NH4Cl and concentrated in vacuo
6. 6
   OtroThe crude reaction mixture
7. 7
   Otrowas purified by reverse-phase preparative HPLC

Procedimiento

To a stirred solution of ((2S,3R)-2-(hydroxymethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone in THF was added NaH (4 equiv.) at 0° C. The reaction was allowed to warm to rt and stirred an additional 30 min. 2-Chloro-5-(trifluoromethyl)pyridine (2 equiv.) was then added and the solution was warmed to reflux for 2 h. The reaction was cooled and quenched with satd. aq. NH4Cl and concentrated in vacuo. The crude reaction mixture was purified by reverse-phase preparative HPLC to afford the title compound. MS (ESI) 460 (M+H).

Fuente