Reacción #9737

Ecuación de reacción

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

Disolventes

ethanol

tetrahydrofuran

cyclohexane

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONthen was added to
2. 2
   workup.WAITAfter 1.5 hours
3. 3
   workup.WAITAfter 2 hours
4. 4
   Otrothe 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
   Otrothe water layer removed
9. 9
   ExtracciónThe aqueous was extracted with 2 further portions of ether
10. 10
    Lavadothe combined organic solution was washed with brine
11. 11
    Secadothen dried (MgSO4)
12. 12
    Concentraciónconcentrated
13. 13
    OtroThe crude product was purified by SPE (silica cartdrige)

Procedimiento

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.

Fuente