Reaktion #72735

Reaktionsgleichung

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

Ausbeute 49.3%

Lösungsmittel

dimethylformamide

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle