Cesium carbonate → 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone

Participants

Reaction Steps

A dispersion of 4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol (intermediate F2.1) (120 mg, 393 μmol), 2-bromo-1-(5-chloropyridin-2-yl)ethanone (101 mg, 432 μmol), cesium carbonate (512 mg, 1.57 mmol), and potassium iodide (2 mg, 14.5 μmol) in acetone (5.51 ml) was stirred at room temperature for 20 hours. For the workup, the reaction mixture was poured into a saturated solution of sodium hydrogencarbonate (5 ml) and extracted with dichloromethane (2×5 ml). The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The crude 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone (165 mg, 92% yield) was obtained as a red gum. MS (ISP): m/z=459.1 [M+H]+.

Provenance & Evidence