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

Temperature

0 °C

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).

1. temperatureThe mixture is warmed
2. temperatureto reflux
3. stirringThe slurry is stirred for 10 minutes
4. temperatureto warm to rt
5. stirringstir an additional 40 min
6. filtrationThe mixture is filtered
7. washthe solid is rinsed with EtOAc and MeOH
8. concentrationThe filtrate is concentrated
9. stirringthe mixture is stirred at rt for 5 h
10. washwashed with saturated aqueous NaHCO3, brine
11. dry with materialdried over Na2SO4
12. concentrationConcentration

ORD record

ord-1875c82f897145ed8ba3994b007c15ee

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541432B2