Sodium Carbonate → 3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-N-((S)-1-methoxypropan-2-yl)benzamide

Participants

Reaction Steps

To a flask was added N-((4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (0.248 g, 0.519 mmol), palladium acetate (5.25 mg, 0.023 mmol), xantphos (0.017 g, 0.029 mmol), and sodium carbonate (0.033 ml, 0.779 mmol) in toluene (1.039 mL). (s)-(+)-1-Methoxy-2-propylamine (0.082 ml, 0.779 mmol) was added. CO gas was bubbled through the reaction mixture for 10 min. The temperature was then brought to 80° C. for 3 h. Then the reaction was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with water, saturated NaHCO3 solution, brine, dried over MgSO4, filtered and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP Ultra silica gel column (50 g), eluting with a gradient of 5-80% EtOAc in hexane, to provide 3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-N-((S)-1-methoxypropan-2-yl)benzamide (0.0591 g, 0.115 mmol, 22.16% yield). MS m/z=514.0 [M+H]+. Calculated for C24H24F5N3O4: 513.17

Provenance & Evidence