Pyridine → HCID 23516247, compound

Participants

Reaction Steps

To a solution of the product of Example 2, Step A, 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid (10.0 g, 24.4 mmol), and pyridine (2.16 mL, 26.8 mmol) in anhydrous dimethylformamide (49 mL) was added pentafluorophenyl trifluoroacetate (5.35 mL, 30.5 mmol). The resultant solution was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with ethyl acetate (600 mL) and washed with 0.1 M aqueous hydrochloric acid (2×240 mL), 25% saturated aqueous sodium bicarbonate (2×240 mL), and saturated brine (240 mL). The organics were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford an oil that was purified on silica gel. Elution with hexanes-ethyl acetate (19:1) afforded 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid pentafluorophenyl ester (12.8 g, 91%) as a pale-yellow powder: m.p. 108.5-110.0° C.; 1H-NMR (400 MHz, CDCl3) δ 8.77 (br s, 1H), 8.07 (br s, 1 H), 7.69 (br s, 1H), 7.48 (br d, J=7.0 Hz, 1H), 6.91 (br d, J=7.2 Hz, 1 H), 6.67 (br s, 1H); 19F-NMR (376 MHz, CDCl3) δ −123.74 (s, 1F), −139.17 (d, J=16.8 Hz, 1F), −152.35 (d, J=21.4 Hz, 2F), −156.96 (t, J=21.4 Hz, 1F), −161.81 (t, J=21.4 Hz, 2F). Anal. Calcd/found for C19H6NO2F7ClI: C, 39.65/39.32; H, 1.05/0.91; N, 2.43/2.35; F, 23.10/22.85; Cl, 6.16/6.92; I, 22.05/22.50. Step C: Preparation of 2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide

Provenance & Evidence