반응 #72735

반응 방정식

5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]oct-3-ene

imidazole

sodium hydride

→

5-[2-(−1H-imidazol-1-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]oct-3-ene

수율 49.3%

용매

dimethylformamide

dimethylformamide

반응 조건

후처리

1. 1
   workup.ADDITIONis introduced into a 10 ml three-necked round-bottomed flask
2. 2
   온도the reaction medium is heated at 85° C. for 15 hours
3. 3
   workup.WAITat 110° C. for 24 hours
4. 4
   기타the solvent is evaporated off under reduced pressure
5. 5
   추출The aqueous phase is extracted again with 10 ml of chloroform
6. 6
   세척the combined organic phases are washed with saturated aqueous sodium chloride solution
7. 7
   건조dried over sodium sulfate
8. 8
   여과filtered
9. 9
   농축concentrated under reduced pressure
10. 10
    기타The residue is purified by chromatography on a column of silica gel
11. 11
    세척eluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions

실험 절차

0.64 g (9.42 mmol) of imidazole dissolved in 3 ml of dimethylformamide is introduced into a 10 ml three-necked round-bottomed flask. 0.415 g (10.4 mmol) of sodium hydride as a 60% dispersion in oil is then added and the mixture is stirred at room temperature for 1 hour. The mixture is then added to a solution of 5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]oct-3-ene (WO 03/057 697) (0.5 g, 1.89 mmol) in dimethylformamide and the reaction medium is heated at 85° C. for 15 hours and then at 110° C. for 24 hours and the solvent is evaporated off under reduced pressure. The residue is taken up in 10 ml of chloroform and 10 ml of saturated aqueous sodium carbonate solution. The aqueous phase is extracted again with 10 ml of chloroform and the combined organic phases are washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica gel, eluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions. 0.235 g of 5-[2-(−1H-imidazol-1-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]oct-3-ene is obtained and is dissolved in 3 ml of isopropyl alcohol to add 0.327 ml of a 5.7N solution of hydrobromic acid in acetic acid. The crystals formed are collected by filtration and dried under vacuum.

출처