Aniline → 4-Chloro-2-[(N-phenylamino)acetamido]benzoic Acid

Participants

Reaction Steps

A solution of 4-chloro-2-(bromoacetamido)benzoic acid from Example 40 (6.5 g, 0.02 mol), aniline (5.2 mL, 250 mol %) and anhydrous DMF (50 mL) was heated to 100°-105° C. for 4h, and stirred at rt for 20h. The reaction mixture was poured into ice-water (400 mL) and the precipitated product was solubilized by adding aqueous 5% KOH (60 mL). The resulting milky homogenous solution was extracted with CH2Cl2 (3×100 mL). The combined CH2Cl2 extracts were set aside and the aqueous layer was acidified with aqueous 5% HBr to pH=3. The resulting oil was extracted into EtOAc (3×100 mL) and the combined extract was washed with brine, dried, filtered and concentrated. Trituration of the resulting solid with diethyl ether afforded 4.5 g (66%) of the crude title compound as light-beige crystals, mp 177.8°-180° C. The crude compound (4.5 g) was stirred with EtOAc (~100 mL) and the resulting insoluble portion was filtered off. The filtrate was concentrated to a light-beige solid which was refluxed with benzene (80 mL) for 40 min. The bnenzene mixture was filtered while hot and the filtered solid was dried for 4 h under high vacuum, yielding 2.75 g (40%) of the title compound as light crystals, mp 229°-230° C. (became "wet" at 227° C.); 1H NMR (DMSO-d6) δ 13.6 (bs, 1H), 12.11 (s, 1H), 8.82 (d, J=1.6, 1H), 7.93 (d, J=8.8, 1H), 720 (dd, J=6.0, J=2.6, 1H), 7.10 (t, J=7.6, 2H) 6.63-6.58 (m, 4H), 3.85 (s, 2H); 13C NMR (DMSO-d6)δ 171.48, 168.31, 148.01, 141.53, 138.58, 132.86, 128.97, 128.30, 122.61, 118.72, 118.67, 117.16, 114.68, 112.45, 48.89.

Provenance & Evidence