反应详情

温度

-70 °C

Propionitrile (1.21 g) in dry tetrahydrofuran (50 ml) was cooled to -72° C. A solution of n-butyllithium in n-hexane (14.2 ml, 1.55 molar) was then slowly added while maintaining the temperature of the reaction mixture at -45° C. or below. After stirring for about 30 minutes, 2-(1H-1,2,4-triazol-1-yl)-2',4'-dichloroacetophenone (2.56 g) in dry tetrahydrofuran (THF) (50 ml) was added slowly with stirring over a 20 minute period, the temperature of the mixture being maintained at -70° C. Stirring was continued at this temperature for one hour and then at -10° for a half hour, then glacial acetic acid (10 ml) in dry THF (15 ml) was added. The reaction mixture was allowed to warm to room temperature (20° C.), adjusted to pH 8 with solid sodium bicarbonate, and extracted with ethyl acetate (3×75 ml). The combined organic extracts were washed three times with water, dried (MgSO4), evaporated and ethyl ether (30 ml) was added to the residue, yielding a white crystalline solid and a yellow solution. The solid was filtered off, dissolved in a small volume of methylene chloride, and loaded onto an 18 g flash chromatography column of Merck's "Kieselgel 60" (Trade Mark) 230-400 mesh silica in ether (11×2 cm. diameter). Elution was carried out using 5% (by volume) acetone in ether at one p.s.i. (0.07 kg/m2) "Diastereoisomer 1" of the title compound was eluted first, 0.79 g, m.p. 178°-180° C.

1. temperaturewhile maintaining the temperature of the reaction mixture at -45° C. or below
2. stirringwith stirring over a 20 minute period
3. stirringStirring
4. waitwas continued at this temperature for one hour
5. waitat -10° for a half hour
6. temperatureto warm to room temperature (20° C.)
7. extractionextracted with ethyl acetate (3×75 ml)
8. washThe combined organic extracts were washed three times with water
9. dry with materialdried (MgSO4)
10. customevaporated
11. additionethyl ether (30 ml) was added to the residue
12. customyielding a white crystalline solid
13. filtrationThe solid was filtered off
14. dissolutiondissolved in a small volume of methylene chloride
15. washElution
16. wash(0.07 kg/m2) "Diastereoisomer 1" of the title compound was eluted first