Pyridine → 4-Chloro-3-[2-(4-isopropyl-3-methyl-phenoxy)-acetylamino]-benzoic acid

Participants

Reaction Steps

A suspension of 2-(4-isopropyl-3-methylphenoxy)acetic acid (1.50 g, 7.2 mmol) and catalytic dimethylformamide (3 drops) in dichloromethane (100 mL) was treated with a solution of oxalyl chloride (1.80 mL, 21.9 mmol) in dichloromethane (10 mL) dropwise over 20 min. After stirring for an additional 4 h, the solution was evaporated and taken up in THF (60 mL). One-half of this solution (ca. 3.6 mmol acid chloride) was added dropwise to an ice-cooled solution of 5-amino-2-chlorobenzoic acid (0.62 g, 3.6 mmol) and pyridine (0.87 mL, 11 mmol) in THF (5 mL). The resulting solution was stirred for 20 h, then partitioned between water and ethyl acetate (100 mL each). The organic layer was washed with 1 N aq. HCl and brine, and the aqueous phases were back-extracted in sequence with ethyl acetate. The extracts were combined, dried over anhydrous magnesium sulfate, filtered and evaporated. The resulting solid was triturated with 1:1 ethyl acetate, refiltered and dried under vacuum to afford the title product (1.20 g, 3.6 mmol, 100%). m.p. 174–175° C. 1H NMR (d6-DMSO): δ 10.28 (1H, s), 8.13 (1H, t, J=1.8 Hz), 7.79 (1H, dt, J=8, 2 Hz), 7.46 (1H, dd, J=8, 2 Hz), 7.13 (1H, dd, J=8, 1.6 Hz), 6.79–6.71 (2H, m), 4.62 (2H, s), 3.00 (1H, m, J=6.6 Hz), 2.25 (3H, s), 1.12 (6H, d, J=6.6 Hz). Mass spectrum (ES+): m/z 364 (33), 362 (100). Elemental analysis: calculated for C19H20ClNO4 C, 63.07; H, 5.57; N, 3.87. observed C, 62.87; H, 5.58; N, 3.67.

Provenance & Evidence