反应详情

Isobutylene (10 ml) is condensed into a solution of 1-[1,1-dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 200 mg) in methylene chloride (10 ml) at -70°. Phosphoric acid (85%, 50 μl) is added and the mixture stirred for 60 minutes. Boron trifluoride etherate (200 μl) is added dropwise and the resulting suspension is stirred 8 hours at reflux and overnight at 20°-25° allowing the isobutylene to evaporate. The suspension is diluted with water and ammonium hydroxide is added until basic to pH paper and then extracted with methylene chloride (3×). The combined extracts are dried over anhydrous potassium carbonate, filtered, and concentrated under reduced pressure to a liquid which is flash chromatographed (silica gel, 230-400 mesh), eluting with methanol/chloroform (3/20). The appropriate fractions are pooled and concentrated to give an oil. The NMR, CMR, IR, and MS (m/e) M+234 support the title compound.

1. stirringthe resulting suspension is stirred 8 hours
2. temperatureat reflux and overnight at 20°-25°
3. customto evaporate
4. additionThe suspension is diluted with water and ammonium hydroxide
5. additionis added until basic
6. extractionextracted with methylene chloride (3×)
7. dry with materialThe combined extracts are dried over anhydrous potassium carbonate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure to a liquid which
10. customchromatographed (silica gel, 230-400 mesh)
11. washeluting with methanol/chloroform (3/20)
12. concentrationconcentrated
13. customto give an oil