反応 #2030774

反応方程式

diethyl azodicarboxylate

caustic soda

triphenylphosphine

4-chloronaphthalen-1-ol

tert-butyl 2-hydroxy-7-aza-spiro[3.5]-nonane-7-carboxylate

→

expected product

2-(4-chloronaphthalen-1-yloxy)-7-aza-spiro[3.5]-nonane hydrochloride

溶媒

toluene

toluene

反応条件

後処理

1. 1
   濃縮concentrated under vacuum
2. 2
   その他The residue obtained
3. 3
   抽出extracted twice with dichloromethane
4. 4
   洗浄The combined organic phases are washed once with a saturated aqueous solution of sodium chloride
5. 5
   乾燥dried over sodium sulphate
6. 6
   ろ過filtered
7. 7
   濃縮concentrated under vacuum
8. 8
   workup.ADDITION10 ml (40 mmoles) of a 4N solution of hydrochloric acid in dioxan are added slowly
9. 9
   workup.STIRRINGwith stirring
10. 10
    workup.STIRRINGAfter stirring for 3 hrs at ambient temperature
11. 11
    濃縮the medium is concentrated under vacuum
12. 12
    抽出The aqueous phase is extracted twice with ethyl acetate
13. 13
    workup.ADDITIONthen slowly basified to pH 10 by addition of 35% caustic soda solution
14. 14
    抽出The aqueous phase is extracted three times with dichloromethane
15. 15
    洗浄washed once with a saturated aqueous solution of sodium chloride
16. 16
    乾燥dried over sodium sulphate
17. 17
    ろ過filtered
18. 18
    濃縮concentrated under vacuum

実験手順

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.

出典