反应详情

温度

0 °C

Diisopropylamine (1.23 g, 12.2 mmole) was dissolved in 150 ml dry THF and the reaction was cooled to 0° C. n-Butyllithium (2.5 ml in Hexane, 4.5 ml, 11.2 mmole) was added and the reaction was stirred at 0° C. for 10 minutes. The reaction was cooled to −100° C. and 4-benzyloxy-2-butanone (1.83 g, 10.3 mmole) in 50 ml dry THF (pre-cooled to −78° C.) was added. The reaction was stirred for 30 minutes at −78° C. 4-(4-Chloro-benzenesulfonyl)-5,8-difluoro-2H-chromene (3.2 g, 9.36 mmole) in 20 ml THF (pre-cooled to −78° C.) was added. The reaction was stirred at −78° C. for 1 hour. 20 ml water was added at −78° C. to quench the reaction. After the reaction was warmed up to room temperature, 200 ml EtOAc was added. The organic layer was washed with brine (2×100 ml), dried over Na2SO4 and concentrated. The product was purified by column chromatography (EtOAc/hexane from 0/100 to 40/60 in 45 minute). Yield, 2.6 g, 53%. 1H NMR (CDCl3 400 MHz δ 7.82 (d, J=8.8 Hz, 2H), 7.54 (d, J=8.1 Hz, 2H), 7.20-7.35 (m, 5H), 7.05 (m, 1H), 6.47 (m, 1H), 4.89 (dd, J=11.7 and 2.9 Hz, 1H), 4.42 (s, 3H), 4.24 (dt, J=12.4 and 2.2 Hz, 1H), 3.65 (t, J=5.9 Hz, 2H), 3.31 (m, 1H), 2.33-2.67 (m, 4H).

1. additionwas added
2. temperatureThe reaction was cooled to −100° C.
3. stirringThe reaction was stirred for 30 minutes at −78° C
4. stirringThe reaction was stirred at −78° C. for 1 hour
5. customto quench
6. customthe reaction
7. temperatureAfter the reaction was warmed up to room temperature
8. washThe organic layer was washed with brine (2×100 ml)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customThe product was purified by column chromatography (EtOAc/hexane from 0/100 to 40/60 in 45 minute)
12. customYield