反应详情

温度

100 °C

A degassed solution of (RS)-5-(3-bromo-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (intermediate XII-1) (100 mg, 0.37 mmol) in 1,2-dimethoxyethane was treated with tetrakis(triphenylphosphine)palladium(0) (42.7 mg, 0.037 mmol), then purged again with argon for 15 minutes. Thereafter, a solution of sodium hydrogencarbonate (1 M, 0.5 ml) and 2,4-difluoro-benzene-boronic acid (116.5 g, 0.74 mmol) were added. The tube was sealed and the mixture heated to 100° C. for 3 hours. For the workup, the reaction mixture was filtered through Celite®, then extracted with dichloromethane (2×15 ml). The combined organic layers were evaporated and the residue was repeatedly (3×) purified by chromatography on a silica-amine phase. The (RS)-5-(2′,4′-difluoro-biphenyl-3-yl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine was obtained as an off-white solid (20 mg, 18% of theory). MS (ISP): m/z=303.4 [M+H]+.

1. custompurged again with argon for 15 minutes
2. customThe tube was sealed
3. filtrationFor the workup, the reaction mixture was filtered through Celite®
4. extractionextracted with dichloromethane (2×15 ml)
5. customThe combined organic layers were evaporated
6. custompurified by chromatography on a silica-amine phase