反应详情

A three-neck two liter flask equipped with dropping funnel, reflux condenser, and mechanical stirrer was charged with 4-[5-(trifluoromethyl)pyridin-2-yl]benzaldehyde (69.00 g, 274.7 mmol) and (S)-(−)-2-methyl-2-propanesulfinamide (33.66 g, 277.7 mmol). The apparatus was purged with dry nitrogen and warmed with a heat gun. The solids were suspended in dichloromethane (1.0 L) whereupon titanium(IV) ethoxide (115 ml, 549 mmol) was added dropwise over 30 minutes during which time the solids dissolved affording a yellow solution. No increase in temperature was observed. The reaction was heated to reflux for 12 hours. The reaction was quenched with a dropwise addition of MeOH (400 mL) followed by saturated aqueous sodium bicarbonate (150 mL). The resulting precipitate was removed by filtration through a pad of 1:1 celite:florisil and the filter cake was washed with ethyl acetate (3×200 ml). The resulting mixture was partially concentrated under vacuum (50% volume) and then dried over magnesium sulfate. The resulting solution was filtered through a Buchner funnel, the salts were washed with ethyl acetate (3×200 ml) and the resulting filtrate was concentrated in vacuo. The crude solid was suspended in heptane (250 ml) and heated to boiling with a heat gun whereupon ethyl acetate was added in aliquots to dissolve the solids. The mixture was then cooled slowly to affect crystallization (slowly to ambient temperature, then with ice). The solids were collected by vacuum filtration, and the process was repeated once more to yield the final product (78.78 g, 81%) as an off-white crystalline solid. 1H NMR (400 MHz, CDCl3, δ): 9.01 (s, 1H), 8.67 (s, 1H), 8.19 (d, J=8.4 Hz, 2H), 8.07 (dd, J=8.4, 2.0 Hz, 1H), 8.01 (d, J=8.4 Hz, 2H), 7.94 (d, J=8.2 Hz, 1H), 1.30 (s, 9H). MS (M+1) 355.1.

1. customA three-neck two liter flask equipped
2. temperaturereflux condenser, and mechanical stirrer
3. customThe apparatus was purged with dry nitrogen
4. temperaturewarmed with a heat gun
5. additionwas added dropwise over 30 minutes during which time the solids
6. dissolutiondissolved
7. customaffording a yellow solution
8. temperatureNo increase in temperature
9. temperatureThe reaction was heated
10. temperatureto reflux for 12 hours
11. customThe reaction was quenched with a dropwise addition of MeOH (400 mL)
12. customThe resulting precipitate was removed by filtration through a pad of 1:1 celite
13. washflorisil and the filter cake was washed with ethyl acetate (3×200 ml)
14. concentrationThe resulting mixture was partially concentrated under vacuum (50% volume)
15. dry with materialdried over magnesium sulfate
16. filtrationThe resulting solution was filtered through a Buchner funnel
17. washthe salts were washed with ethyl acetate (3×200 ml)
18. concentrationthe resulting filtrate was concentrated in vacuo
19. temperatureheated
20. additionwas added in aliquots
21. dissolutionto dissolve the solids
22. temperatureThe mixture was then cooled slowly
23. customcrystallization (slowly to ambient temperature
24. filtrationThe solids were collected by vacuum filtration