Sodium Bicarbonate → Benzyl 4-{4-[3-(2,5-difluorophenoxy)propylamino]phenyl}-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

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Reaction Conditions

Reaction Steps

A baked-out Schlenk flask is initially charged with 0.350 g of chloro(di-2-norbomylphosphino)(2-dimethylaminomethylferrocen-1-yl)palladium(II). Under argon, a solution of 0.520 g of benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-trifluoromethanesulphonyloxyphenyl)piperidine-1-carboxylate (Example 265b) and 0.172 g of 3-(2,5-difluorophenoxy)propylamine in 5.3 ml of dried dioxane is added. The reaction mixture is stirred at room temperature over 30 minutes and subsequently at 100° C. over 18 hours. The reaction mixture is cooled, poured onto aqueous 1M sodium hydrogencarbonate solution (20 ml) and extracted with tert-butyl methyl ether (2×20 ml). The organic phases are washed with brine (1×20 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.29 (2:1 EtOAc-heptane); Rt=4.91.

Provenance & Evidence