Hydrochloric Acid → 6-(4-{[3-(2,6-Dichlorophenyl)-5-(1-Methylethyl)isoxazol-4-Yl]methoxy}phenyl)quinoline-2-Carboxylic Acid

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Reaction Steps

A stirred mixture of methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (245 g, 0.45 mol), NaOH (36 g, 0.90 mol) dissolved in water (225 mL), methanol (0.5 L) and THF (1.2 L) was heated at 65° C. for 90 min. The mixture was cooled to room temperature, treated with 6 N HCl (150 mL) and stirred at room temperature for 30 min. The resulting precipitate was collected by filtering, washed with water (2×1 L) and dried overnight at 45° C. in a vacuum oven to yield 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid (162 g, 68%). A second crop of material was similarly obtained (27.2 g, 11%). 1H NMR (400 MHz, DMSO-d6): 8.48 (d, J=9 Hz, 1H), 8.24 (d, J=2 Hz, 1H), 8.17 (d, J=9 Hz, 1H), 8.09 (d, J=9 Hz, 2H), 7.72 (d, J=9 Hz, 2H), 7.62 (d, J=8 Hz, 2H), 7.53 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.88 (s, 2H), 3.46 (m, 1H), 1.32 (d, J=7 Hz, 6H). ES-LCMS m/z 533 (M+H)+.

Provenance & Evidence