3,5-Bis(trifluoromethyl)benzylamine → Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate

Participants

Reaction Conditions

Reaction Steps

Tert-butyl 4-(2-chloropyrimidin-5-yloxy)-butyrate (5.0 g) is dissolved in toluene (100 ml) and thereto are added palladium acetate (412 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.26 g), and the mixture is stirred under nitrogen atmosphere at 50° C. for 1 hour. The reaction solution is cooled to room temperature, and thereto are added 3,5-bis-trifluoromethyl-benzylamine (5.35 g) and sodium tert-butoxide (3.88 g) and the mixture is stirred at 35° C. for 2 hours. Thereto are added ethyl acetate and water, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→2:1) and NH-silica gel column chromatography (hexane:ethyl acetate=4:1→2:1) to give tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (5.59 g). MS (m/z): 480 [M+H]+

Provenance & Evidence