反应详情

温度

140 °C

DIPEA (46.4 g, 360 mmol) was added to ethyl [(3S)-7-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-yl]acetate (Intermediate 27a, 36 g, 120 mmol), 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid (28 g, 144 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% solution in EtOAc) (152.6 g, 240 mmol) in butyl acetate (100 mL) at rt. The resulting suspension was stirred at 140° C. for 2 hours. The reaction mixture was diluted with EtOAc (700 mL) and washed with saturated NaHCO3 (500 mL), 1 M HCl (500 mL) and brine (500 mL). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to afford crude product. The residue was purified by a silica chromatography, eluent gradient from 5% to 20% of EtOAc in PE. The pure fraction was evaporated to dryness to afford title compound (33 g, 58%) as an off-white solid.

1. washwashed with saturated NaHCO3 (500 mL), 1 M HCl (500 mL) and brine (500 mL)
2. dry with materialThe organic layer was dried over anhydrous Na2SO4
3. filtrationfiltered
4. customevaporated
5. customto afford crude product
6. customThe residue was purified by a silica chromatography, eluent gradient from 5% to 20% of EtOAc in PE
7. customThe pure fraction was evaporated to dryness