反应详情

温度

-78 °C

A flask charged with 6.43 mL of dimethyl t-butoxycarbonyl-methylphosphonate (32 mmol) in 50 mL of dry THF/DMPU (10:1) was cooled to −78° C. where 12.8 mL of n-butyl lithium (2.5M hexane solution, 32 mmol) was added slowly via syringe. The reaction mixture was stirred at −78° C. for 10 minutes and then a solution of 4.4 g of Compound 1D (10.6 mmol) in 30 mL of dry THF was added. After warming to room temperature and an additional 20 minutes of stirring, the reaction was quenched with 30 mL of water and then partitioned with 30 mL of saturated ammonium chloride and 150 mL of ethyl acetate. The water layer was further extracted with ethyl acetate (2×75 mL) and the combined organic layers were then washed with brine (50 mL), dried over magnesium sulfate, filtered and excess solvent was removed on the rotary evaporator. The crude product was purified by flash chromatography (EtOAc/Hexanes; gradient 15% to 30%) to give 3.6 g (96%) of product Compound 1E as a white solid. MS (electrospray): mass calculated for C29H34F3NO4, 517.24; m/z found 518.4, [M+H]+. 1HNMR (300 MHz, CDCl3): 7.56 (d, J=16.5 Hz, 1H), 7.52 (dd, J=2.0, 8.5 Hz, 1H), 7.38 (d, J=2.01 Hz, 1H), 7.16 (s, 1H), 6.98 (d, J=8.5 Hz, 1H), 6.82 (s, 1H), 6.30 (d, J=16.5 Hz, 1H), 4.31 (q, J=8.0 Hz, 2H), 3.99 (q, J=5.1 Hz, 2H), 2.51 (s, 2H), 2.13 (s, 3H), 1.52 (s, 9H), 1.32 (s, 6H), 1.21 (t, J=7.07 Hz, 3H).

1. additionwas added slowly via syringe
2. temperatureAfter warming to room temperature and an additional 20 minutes
3. stirringof stirring
4. customthe reaction was quenched with 30 mL of water
5. custompartitioned with 30 mL of saturated ammonium chloride and 150 mL of ethyl acetate
6. extractionThe water layer was further extracted with ethyl acetate (2×75 mL)
7. washthe combined organic layers were then washed with brine (50 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customexcess solvent was removed on the rotary evaporator
11. customThe crude product was purified by flash chromatography (EtOAc/Hexanes; gradient 15% to 30%)