Reacción #156747

Ecuación de reacción

4-(2-chloro-2,2-difluoroethyl)-1-(chloromethyl)pyrrolidin-2-one

2-[(benzyloxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole

→

4-(2-chloro-2,2-difluoroethyl)-1-{[2-(hydroxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one

Rendimiento 36.0%

Disolventes

dioxane

dioxane

trifluoroacetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   Otro1,4-dioxane is removed under reduced pressure
2. 2
   OtroThe crude reaction mixture
3. 3
   Temperaturaheated at 60° C. for 2 hours
4. 4
   TemperaturaAfter cooling
5. 5
   Otrothe trifluoro-acetic acid is removed under reduced pressure
6. 6
   OtroThe residue is purified by chromatography on silicagel (MeOH/CH2Cl2)

Procedimiento

A solution of 4-(2-chloro-2,2-difluoroethyl)-1-(chloromethyl)pyrrolidin-2-one a18 in dioxane (5 ml) is added to a hot solution (90° C.) of dry ZnCl2 (0.272 g, 2 mmol, 0.5 eq) and 2-[(benzyloxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole a29 (1.3 g, 4 mmol, 1 eq) in dioxane (5 ml). The reaction mixture is heated at 90° C. for 3 days and 1,4-dioxane is removed under reduced pressure. The crude reaction mixture is taken up in trifluoroacetic acid (20 ml) and heated at 60° C. for 2 hours. After cooling, the trifluoro-acetic acid is removed under reduced pressure. The residue is purified by chromatography on silicagel (MeOH/CH2Cl2) and pure 4-(2-chloro-2,2-difluoroethyl)-1-{[2-(hydroxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one 7 (573 mg) is obtained after re-crystallization from ethyl acetate.

Fuente