반응 #9737

반응 방정식

sodium borohydride

N-(tert-butyl)-N,3-dimethyl-4-[4-(trifluoromethyl)phenyl]thiophene-2-carboxamide

intermediate 40

N-(tert-butyl)-N,3-dimethyl-4-[4-(trifluoromethyl)phenyl]thiophene-2-carboxamide

n-Butyllithium

diisobutylaluminium hydride

→

title compound

{3-methyl-4-[4-(trifluoromethyl)phenyl]thien-2-yl}methanol

용매

ethanol

tetrahydrofuran

cyclohexane

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.ADDITIONthen was added to
2. 2
   workup.WAITAfter 1.5 hours
3. 3
   workup.WAITAfter 2 hours
4. 4
   기타the reaction was quenched with wet tetrahydrofuran
5. 5
   workup.ADDITION2M aqueous hydrochloric acid was added
6. 6
   workup.STIRRINGthe mixture was stirred for 15 minutes
7. 7
   workup.ADDITIONEther was added
8. 8
   기타the water layer removed
9. 9
   추출The aqueous was extracted with 2 further portions of ether
10. 10
    세척the combined organic solution was washed with brine
11. 11
    건조then dried (MgSO4)
12. 12
    농축concentrated
13. 13
    기타The crude product was purified by SPE (silica cartdrige)

실험 절차

n-Butyllithium (1.6M in hexanes, 1.1 ml) was added dropwise to a mixture of 1M diisobutylaluminium hydride in cyclohexane (1.77 ml) and tetrahydrofuran at 0° C. under nitrogen. This mixture was allowed to stir for 30 minutes then was added to a cooled (0° C.) solution of N-(tert-butyl)-N,3-dimethyl-4-[4-(trifluoromethyl)phenyl]thiophene-2-carboxamide (intermediate 40, 0.210 g) in tetrahydrofuran (2.5 ml) under nitrogen. After 1.5 hours, a solution of sodium borohydride (0.68 g) in ethanol (5 ml) was added and the reaction was allowed to warm to room temperature. After 2 hours, the reaction was quenched with wet tetrahydrofuran then 2M aqueous hydrochloric acid was added and the mixture was stirred for 15 minutes. Ether was added and the water layer removed. The aqueous was extracted with 2 further portions of ether then the combined organic solution was washed with brine then dried (MgSO4) and concentrated. The crude product was purified by SPE (silica cartdrige) using cyclohexane:ethyl acetate (3:1) as eluent to furnish the title compound as a colourless oil.

출처