Reacción #73339

Ecuación de reacción

imidazole

TBSCl

EtOAc

3-Amino-5-trifluoromethyl-benzoic acid

LiAlH4

NaF

→

title compound

3-(tert-Butyl-dimethyl-silanyloxymethyl)-5-trifluoromethyl-phenylamine

Disolventes

H2O

DCM

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture is warmed
2. 2
   Temperaturato reflux
3. 3
   workup.STIRRINGThe slurry is stirred for 10 minutes
4. 4
   Temperaturato warm to rt
5. 5
   workup.STIRRINGstir an additional 40 min
6. 6
   FiltraciónThe mixture is filtered
7. 7
   Lavadothe solid is rinsed with EtOAc and MeOH
8. 8
   ConcentraciónThe filtrate is concentrated
9. 9
   workup.STIRRINGthe mixture is stirred at rt for 5 h
10. 10
    Lavadowashed with saturated aqueous NaHCO3, brine
11. 11
    Secadodried over Na2SO4
12. 12
    ConcentraciónConcentration

Procedimiento

To a solution of 3-Amino-5-trifluoromethyl-benzoic acid (2.0 g, 9.76 mmol) in THF (40 mL) at 0° C. is added LiAlH4 in THF (1 M, 39 mL). The mixture is warmed to reflux and stirred for 62 h. The mixture is then cooled to 0° C. and NaF (2.2 g) is added followed by H2O (3.8 mL). The slurry is stirred for 10 minutes and then allowed to warm to rt and stir an additional 40 min. The mixture is filtered and the solid is rinsed with EtOAc and MeOH. The filtrate is concentrated and the crude residue is mixed with imidazole (2.66 g, 39 mmol) and DCM (30 mL) at 0° C. TBSCl (3.5 g, 23.4 mmol) is added and the mixture is stirred at rt for 5 h. The reaction mixture is then diluted with EtOAc, washed with saturated aqueous NaHCO3, brine, and dried over Na2SO4. Concentration provides the title compound that is carried on to next step without further purification. MS (ESI) m/z 306.1 (M+1).

Fuente