反应详情

温度

-70 °C

To a solution of 2-methyl-2-(2-methyl-1-pyrrolidinyl)propanenitrile D25 (2.82 g; 18.56 mmol) in THF (100 ml) at −70° C. under argon was added over 15 minutes a solution of phenyllithium in dibutylether (20.6 ml of a 1.8M solution; 37.11 mmol). The reaction mixture was stirred at −70° C. for 2 hours then allowed to warm to room temperature and stirred overnight. Saturated aqueous sodium hydrogen carbonate (100 ml) was added and stirring continued for a further 10 minutes. The mixture was extracted with diethyl ether (2×150 ml). Combined organics were dried (Na2SO4) and evaporated in vacuo. The residual yellow oil was dissolved in methanol (100 ml) and sodium borohydride (2.12 g; 0.056 mol) added portionwise over 5 minutes. The reaction mixture was stirred at room temperature for 4 hours, further sodium borohydride (1 g; 0.026 mol) added and the mixture heated at 60° C. for 1.5 hours. The mixture was cooled and excess sodium borohydride decomposed by dropwise addition of water. The reaction mixture was evaporated in vacuo and the residue partitioned between saturated sodium hydrogen carbonate (150 ml) and DCM (150 ml). Solid potassium carbonate was added and the aqueous layer extracted with DCM (150 ml) Combined organic extracts were dried (Na2SO4) and evaporated to give a green oil. This was divided into 8 portions and each portion passed down a 10 g SCX column. After washing each column with DCM, 50% DCM in methanol and methanol the product was eluted with 1 M ammonia in methanol to yield the title compound as a pale yellow oil (3.46 g: 80%). Mass spectrum (Electrospray LC/MS), ES+: Found 233 (MH+). C15H24N2 requires 232. Ret. times 0.96 and 1.07 min.

1. temperatureto warm to room temperature
2. stirringstirred overnight
3. stirringstirring
4. waitcontinued for a further 10 minutes
5. extractionThe mixture was extracted with diethyl ether (2×150 ml)
6. dry with materialCombined organics were dried (Na2SO4)
7. customevaporated in vacuo
8. dissolutionThe residual yellow oil was dissolved in methanol (100 ml)
9. stirringThe reaction mixture was stirred at room temperature for 4 hours
10. temperaturethe mixture heated at 60° C. for 1.5 hours
11. temperatureThe mixture was cooled
12. customThe reaction mixture was evaporated in vacuo
13. customthe residue partitioned between saturated sodium hydrogen carbonate (150 ml) and DCM (150 ml)
14. additionSolid potassium carbonate was added
15. extractionthe aqueous layer extracted with DCM (150 ml)
16. dry with materialwere dried (Na2SO4)
17. customevaporated
18. customto give a green oil
19. washAfter washing each column with DCM, 50% DCM in methanol and methanol the product
20. washwas eluted with 1 M ammonia in methanol