反应详情

Diethylaminosulphur trifluoride (0.42 g, 2.62 mmol) was added to a stirred solution of 3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptan-3-ol (0.5 g, 2.62 mmol) in dichloromethane (30 ml), at -65° C. After 24 h, water (20 ml) was added, basified with potassium carbonate, and extracted into dichloromethane (3×50 ml). The combined extracts were dried (Na2SO4), evaporated, and the residue chromatographed through silica-gel, eluting with dichloromethane-methanol (90:10) to give 3-fluoro-3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptane (75 mg). The compound was further purified as the hydrogen chloride salt, m.p. 245° C. (dec.) (isopropylalcohol); (Found: C, 52.33; H, 5.79; N, 17.97. C10H12F.HCl requires C, 52.29; H, 5.66; N, 18.30%) m/e 193 (M+ for free base); δ(360 MHz, CDCl3) 1.06-1.13 (1H, m, CH of CH2 --N); 1.44-1.55 (1H, m, CH of CH2 --N); 2.58 (1H, dd, J=3.1 and 9.7 Hz, CH of CH2 --N); 2.65-2.72 (1H, m, CH of CH2 --N); 2.83-2.91 (2H, m, CH-bridgehead and CH of CH2 --N); 3.09-3.24 (2H, m, 2 of CH of CH2 --N); 3.59 (1H, ddd, J=3.1, 13.6 and 20.8 Hz, CH of CH2 --N); 8.50-8.53 (2H, m, 2 of pyrazine-H); 8.91 (1H, d, J=1.2 Hz, pyrazine-H).

1. extractionextracted into dichloromethane (3×50 ml)
2. dry with materialThe combined extracts were dried (Na2SO4)
3. customevaporated
4. customthe residue chromatographed through silica-gel
5. washeluting with dichloromethane-methanol (90:10)