反应详情

温度

0 °C

Under an inert atmosphere, 1.00 g (4.14 mmoles) of tert-butyl 2-hydroxy-7-aza-spiro[3.5]-nonane-7-carboxylate (WO 2003084948) is dissolved in 41 ml of toluene. 1.250 g (4.77 mmoles) of triphenylphosphine and 0.888 g (4.97 mmoles) of 4-chloronaphthalen-1-ol (commercial) are added. The medium is cooled to 0° C. and a solution of 0.794 g (4.56 mmoles) of diethyl azodicarboxylate in 3 ml of toluene is added. The medium is stirred for 14 hrs at ambient temperature, then concentrated under vacuum. The residue obtained is taken up in a 1N aqueous solution of caustic soda and extracted twice with dichloromethane. The combined organic phases are washed once with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered and concentrated under vacuum. The crude residue is taken up in 20 ml of dichloromethane and 10 ml (40 mmoles) of a 4N solution of hydrochloric acid in dioxan are added slowly with stirring. After stirring for 3 hrs at ambient temperature, the medium is concentrated under vacuum and the residue is taken up in a 1N aqueous solution of hydrochloric acid. The aqueous phase is extracted twice with ethyl acetate then slowly basified to pH 10 by addition of 35% caustic soda solution. The aqueous phase is extracted three times with dichloromethane. These three organic extracts are combined, washed once with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered and concentrated under vacuum. The expected product is obtained in the form of a wax which is taken up in 2 ml of a 4N solution of hydrochloric acid in dioxan. The medium is diluted with diethyl ether and the precipitate formed is filtered off, rinsed with diethyl ether and dried under vacuum. 1.10 g of the hydrochloride of the expected product is obtained in the form of a white powder.

1. concentrationconcentrated under vacuum
2. customThe residue obtained
3. extractionextracted twice with dichloromethane
4. washThe combined organic phases are washed once with a saturated aqueous solution of sodium chloride
5. dry with materialdried over sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. addition10 ml (40 mmoles) of a 4N solution of hydrochloric acid in dioxan are added slowly
9. stirringwith stirring
10. stirringAfter stirring for 3 hrs at ambient temperature
11. concentrationthe medium is concentrated under vacuum
12. extractionThe aqueous phase is extracted twice with ethyl acetate
13. additionthen slowly basified to pH 10 by addition of 35% caustic soda solution
14. extractionThe aqueous phase is extracted three times with dichloromethane
15. washwashed once with a saturated aqueous solution of sodium chloride
16. dry with materialdried over sodium sulphate
17. filtrationfiltered
18. concentrationconcentrated under vacuum