反应详情

温度

117 °C

In a 250 mL 3-necked flask, ethyl [(3S)-7-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-yl]acetate (Intermediate 27a, 4.2 g, 14.0 mmol) and 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid (2.73 g, 14.1 mmol) were suspended in butyl acetate (40 mL). DIPEA (7.31 mL, 42.0 mmol) was added followed by T3P (50% in BuOAc) (17.8 g, 28.0 mmol). The reaction was heated in an alumina block for 7 h at 117° C. (internal reaction temp. the heating block was set to 135° C.). The reaction was allowed to cool to r.t over night. The crude reaction was diluted with EtOAc (150 mL) and washed with sat. aq. NaHCO3 (100+30 mL), 1 M citric acid aq. (50 mL), 1 M HCl (50 mL) and brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated to afford crude product as a red and foamy oil. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. A gradient from 30% to 75% of EtOAc in heptane over 5 CV was used as mobile phase. The product was collected using the wavelengths 254/280 nm. The title compound (4.23 g, 63.6%) was obtained as a foamy solid.

1. customwas set to 135° C.
2. temperatureto cool
3. waitto r.t over night
4. customThe crude reaction
5. washwashed with sat. aq. NaHCO3 (100+30 mL), 1 M citric acid aq. (50 mL), 1 M HCl (50 mL) and brine (100 mL)
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford crude product as a red and foamy oil
10. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column
11. customThe product was collected