反应详情

A 12 L, 3-neck round bottom flask was equipped with a mechanical stirrer, condenser, thermometer and heating mantle. The flask was flushed with nitrogen and charged with diethyl phosphite (554 g, 3.77 mol), paraformaldehyde (142 g, 4.72 mol), toluene (2 L) and triethylamine (53 mL, 5.76 mol). The mixture was stirred at 85-90° for 2 h, then at reflux for 1 h. The resulting yellow solution was cooled to 4° C. (ice bath) and p-toluenesulfonyl chloride (718 g, 3.77 mol) was added. The condenser was replaced with an addition funnel and triethylamine (750 mL) was added slowly with stirring, maintaining the temperature <10° C. After the addition was complete (45 min.), the resulting mixture was stirred at ambient temperature for 14 h. The mixture was filtered and the filtercake was washed with toluene (2×250 mL). The combined filtrate and washings were washed with water (2×1 L, dried (MgSO4, 200 g), filtered through Celite 521, and concentrated under reduced pressure to provide 1004 g of a cloudy yellow oil (77.6%). 1H NMR (CDCl3): NMR (DMSO): 7.82 (d, J=8.2 Hz, 2H), 7.48 (d, J=8.2 Hz, 2H), 4.36 (d, J=9.6 Hz, 2H), 4.00 (m, 4H), 2.41 (s, 3H), 1.16 (m, 6H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=40% EtOAc/hexanes, Rf=0.24.

1. customA 12 L, 3-neck round bottom flask was equipped with a mechanical stirrer, condenser
2. temperaturethermometer and heating mantle
3. customThe flask was flushed with nitrogen
4. temperatureat reflux for 1 h
5. additionwas added
6. customThe condenser was replaced with an addition funnel
7. stirringwith stirring
8. temperaturemaintaining the temperature <10° C
9. additionAfter the addition
10. custom(45 min.)
11. stirringthe resulting mixture was stirred at ambient temperature for 14 h
12. filtrationThe mixture was filtered
13. washthe filtercake was washed with toluene (2×250 mL)
14. washThe combined filtrate and washings were washed with water (2×1 L
15. dry with materialdried (MgSO4, 200 g)
16. filtrationfiltered through Celite 521
17. concentrationconcentrated under reduced pressure