反应详情

A baked-out Schlenk flask is initially charged under argon with 0.071 g of tri-tert-butylphosphine and 0.114 g of palladium trifluoroacetate. 1.3 ml of degassed toluene are added and the suspension is stirred under argon over 10 minutes. 0.700 g of benzyl 4-[4-(azetidin-3-yloxy)phenyl]-3-[4-(3-methoxypropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate (Example 257c), 0.265 g of tribasic potassium phosphate and 0.290 ml of bromothiazole are added and the reaction mixture is stirred at 80-85° C. over 16 hours. The reaction mixture is cooled, diluted with 20 ml each of brine and water and subsequently extracted with 40 ml of ethyl acetate. The organic phase is dried with sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellow resin from the residue by means of flash chromatography (SiO2 60F). Rf=0.15 (4:1 EtOAc-heptane); Rt=4.34.

1. stirringthe reaction mixture is stirred at 80-85° C. over 16 hours
2. temperatureThe reaction mixture is cooled
3. extractionsubsequently extracted with 40 ml of ethyl acetate
4. dry with materialThe organic phase is dried with sodium sulphate
5. filtrationfiltered
6. concentrationconcentrated by evaporation