Reaktion #156741
ord-0449c6b96d814aa493b8c1679b9734d1
Reaktionsgleichung
Edukte
Reagenzien
Reaktionsbedingungen
Aufarbeitung
- 1Temperaturfurther heating of the reaction mixture
- 2Temperaturat reflux for 3 days
- 3TemperaturAfter cooling
- 4Extraktionthe crude mixture is extracted by CH2Cl2 (2×250 ml)
- 5TrocknenThe cumulated organic layers are dried over MgSO4
- 6Filtrationfiltered
- 7Sonstigecondensed under reduced pressure
- 8SonstigeThe residue is purified over silicagel (eluent: CH2Cl2/MeOH/NH4OH 99/1/0.1)
Vorschrift
To a hot solution (80° C.) of ZnCl2 (0.23 g, 1.69 mmol, 10 mol %) and 2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole a28 (4 g, 16.96 mmol) in dioxane (200 ml) is added a solution of 4-(2-chloro-2,2-difluoroethyl)-1-(chloromethyl)pyrrolidin-2-one a18 in dioxane (5 ml). The reaction mixture is heated at 85° C. for 5 days, then a further 2 g of pyrrolidinone a18 is added in one portion and the reaction mixture is kept under agitation at 90° C. for 1 day. A further addition of pyrrolidinone a18 (2 g) in order to insure complete conversion of compound a28 and further heating of the reaction mixture at reflux for 3 days increased significatively the conversion of imidazo[2,1-b][1,3,4]thiadiazole a28. After cooling and hydrolysis (250 ml of water), the crude mixture is extracted by CH2Cl2 (2×250 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified over silicagel (eluent: CH2Cl2/MeOH/NH4OH 99/1/0.1) to afford 4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one 4.