反应详情

A solution of isopropylamine (45.0 ml) in acetonitrile (250 ml) was cooled to 10° C. and hydrogen chloride gas introduced into the solution keeping the temperature below 15° C. to pH 8.5±0.3. The resultant slurry was allowed to warm to room temperature and sodium cyanoborohydride (12.0 g) added in one portion and the pH readjusted to 8.5 if necessary. 6'-Hydroxyspiro-(9H-fluorene-9,3'-piperidine)-2'-one (30.0 g) was then added and the reaction mixture heated to reflux for 2 hours. The mixture was allowed to cool to room temperature and dilute hydrochloride acid added to pH 1-2 to destroy any excess cyanoborohydride. The acetonitrile was removed under reduced pressure and the residue basified with sodium hydroxide solution (pH 11) and extracted with dichloromethane (3×100 ml) and the combined organic layers washed with sodium hydroxide solution, dried with anhydrous sodium sulphate and evaporated to give the crystalline free amine.

1. customthe temperature below 15° C.
2. temperaturethe reaction mixture heated
3. temperatureto reflux for 2 hours
4. temperatureto cool to room temperature
5. customto destroy any excess cyanoborohydride
6. customThe acetonitrile was removed under reduced pressure
7. extractionextracted with dichloromethane (3×100 ml)
8. washthe combined organic layers washed with sodium hydroxide solution
9. dry with materialdried with anhydrous sodium sulphate
10. customevaporated