반응 #49085

반응 방정식

sodium hydrogen carbonate

sodium borohydride

sodium borohydride

2-methyl-2-(2-methyl-1-pyrrolidinyl)propanenitrile

phenyllithium

sodium borohydride

→

title compound

수율 80.0%

(±)[2-Methyl-2-(2-methyl-1-pyrrolidinyl)-1-phenylpropyl]amine

수율 80.0%

용매

water

THF

dibutylether

반응 조건

후처리

1. 1
   온도to warm to room temperature
2. 2
   workup.STIRRINGstirred overnight
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITcontinued for a further 10 minutes
5. 5
   추출The mixture was extracted with diethyl ether (2×150 ml)
6. 6
   건조Combined organics were dried (Na2SO4)
7. 7
   기타evaporated in vacuo
8. 8
   workup.DISSOLUTIONThe residual yellow oil was dissolved in methanol (100 ml)
9. 9
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 4 hours
10. 10
    온도the mixture heated at 60° C. for 1.5 hours
11. 11
    온도The mixture was cooled
12. 12
    기타The reaction mixture was evaporated in vacuo
13. 13
    기타the residue partitioned between saturated sodium hydrogen carbonate (150 ml) and DCM (150 ml)
14. 14
    workup.ADDITIONSolid potassium carbonate was added
15. 15
    추출the aqueous layer extracted with DCM (150 ml)
16. 16
    건조were dried (Na2SO4)
17. 17
    기타evaporated
18. 18
    기타to give a green oil
19. 19
    세척After washing each column with DCM, 50% DCM in methanol and methanol the product
20. 20
    세척was eluted with 1 M ammonia in methanol

실험 절차

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.

출처