Sodium Hydroxide → HCID 87263219, compound

Participants

Reaction Steps

1-[2-(Cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethanol (500 mg) is dissolved in methylene chloride (5 ml) and thereto is added thionyl chloride (133 μl) under ice-cooling and the mixture is stirred at room temperature for 15 minutes. To the reaction solution are added methylene chloride and a saturated aqueous sodium bicarbonate solution, 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 resulting residue and ethyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (749 mg) are dissolved in N,N-dimethylformamide (5 ml) and thereto is added sodium hydride (62%) (64 mg) under ice-cooling and the mixture is stirred for 1 hour. Thereto are added water and ethyl acetate, 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 resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:14:1) to give ethyl 4-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yloxy]-butyrate (144 mg) as a crude product. The resulting ester is dissolved in ethanol (2 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (500 μl) and the mixture is stirred at room temperature for 2 hours and concentrated under reduced pressure. To the residue is added ethyl acetate and a dilute hydrochloric acid 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 resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→24:1) to give 4-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yloxy]-butyric acid (11 mg). MS (m/z): 707 [M+H]+

Provenance & Evidence