反应详情

温度

-20 °C

Dry ethyl ether (500 mL), n-BuLi (1.6M in hexane, 62.5 mL, 0.1 mol), and dry 1,4-diazabicyclo[2.2.2]octane (DABCO) (11.56 g, 0.1 mol) were introduced into a 1 L flask under a dry N2 stream at -60° C. and the resulting cloudy solution was stirred for 1 hour at -20° C. The mixture was then cooled to -75° C. and an ethyl ether (50 mL) solution of 3-fluoropyridine (9.81 g, 0.1 mol) was added dropwise and stirring continued for 11/2 hours at -60° C. The mixture was recooled to -75° C., dry N,N-dimethylformamide (8.52 mL, 0.11 mol) dissolved in ethyl ether (50 mL) was added dropwise and the mixture stirred for 2 hours at -75° C. Water (175 mL) was introduced slowly at -10° C., the aqueous layer extracted with ethyl acetate (5×200 mL), and the combined extracts were dried over anhydrous sodium sulfate. Solvent removal produced a dark brown oil which after vacuum distillation and purification by chromatography on silica gel provided 4.4 g (35%) of the titled product as an off-white crystalline solid:

1. customstream at -60° C.
2. temperatureThe mixture was then cooled to -75° C.
3. stirringstirring
4. custom2 hours
5. customat -60° C
6. customwas recooled to -75° C.
7. additionwas added dropwise
8. stirringthe mixture stirred for 2 hours at -75° C
9. extractionthe aqueous layer extracted with ethyl acetate (5×200 mL)
10. dry with materialthe combined extracts were dried over anhydrous sodium sulfate
11. customSolvent removal
12. customproduced a dark brown oil which
13. distillationafter vacuum distillation and purification by chromatography on silica gel