反应详情

温度

-10 °C

Sodium hydride (1.4 g, 57.1 mmol) was suspended in THF (50 mL) in a pressure flask under a nitrogen atmosphere and cooled to −10° C. with stirring. Ethyl (1,1-diethoxyethyl)phosphinate (10.0 g, 47.6 mmol) in THF (20 mL) was added dropwise to the mixture over 10 minutes; the internal temperature was maintained below 0° C. during the addition. On completion of addition, the reaction mixture was allowed to stir at this temperature for 90 minutes. The flask was cooled to −78° C. and chlorofluoromethane gas (9.7 g, 142.8 mmol) was condensed into the reaction mixture. The septum was removed and the flask was sealed with a screw thread stopper. The flask was then allowed to warm to room temperature and then heated at 50° C. for 24 h. The reaction mixture was cooled to 0° C. and cautiously quenched with water (25 mL). Methylene chloride (50 mL) was added to the reaction mixture and the emulsion was filtered through a pad of Celite® (20 g). The aqueous phase was extracted with methylene chloride (2×100 mL), dried over anhydrous magnesium sulfate, and the organic phase was concentrated under reduced pressure affording the crude product as a pale yellow oil (6.93 g). The crude residue was purified by silica gel column chromatography (6×25 cm column) eluting with 20% acetone in hexanes. This procedure afforded ethyl (fluoromethyl)(1,1-diethoxyethyl)phosphinate as a clear, colorless oil (4.4 g, 42%). 1H NMR (300 MHz, CDCl3) δ 4.94-4.54 (m, 2H), 4.32-4.20 (m, 2H), 3.82-3.54 (m, 4H), 1.60-1.44 (m, 3H), 1.40-1.28 (m, 3H), 1.26-1.08 (m, 6H).

1. temperaturethe internal temperature was maintained below 0° C. during the addition
2. additionOn completion of addition
3. stirringto stir at this temperature for 90 minutes
4. temperatureThe flask was cooled to −78° C.
5. customcondensed into the reaction mixture
6. customThe septum was removed
7. customthe flask was sealed with a screw thread stopper
8. temperatureto warm to room temperature
9. temperatureheated at 50° C. for 24 h
10. temperatureThe reaction mixture was cooled to 0° C.
11. customcautiously quenched with water (25 mL)
12. additionMethylene chloride (50 mL) was added to the reaction mixture
13. filtrationthe emulsion was filtered through a pad of Celite® (20 g)
14. extractionThe aqueous phase was extracted with methylene chloride (2×100 mL)
15. dry with materialdried over anhydrous magnesium sulfate
16. concentrationthe organic phase was concentrated under reduced pressure
17. customaffording the crude product as a pale yellow oil (6.93 g)
18. customThe crude residue was purified by silica gel column chromatography (6×25 cm column)
19. washeluting with 20% acetone in hexanes