Hydrochloric Acid → HCID 22025610, compound

Participants

Reaction Steps

Methyl 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoate (1.00 g), 2.45 mmol) and (Ph3P)4Pd (568 mg, 0.49 mmol) were weighed into a dry flask which was fitted with a condensor and flushed with nitrogen. Dioxane (20 mL) and allyltributyltin (976 mg, 2.95 mmol) were added via syringe and the entire mixture heated at reflux overnight. All solvent was removed under reduced pressure and the residue loaded directly onto a silica gel column (10% EtOAc/PE as eluant). After chromatography, the crude methyl ester was obtained as a pale yellow oil which was dissolved in a mixture of EtOH (25 mL) and 1 M NaOH (25 mL) and stirred overnight at RT. The mixture was then diluted with water (70 mL) and acidified with 1 M HCl (approx. 30 mL), then extracted with EtOAc (3×100 mL). The combined EtOAc fractions were washed with water (100 mL), brine (100 mL), dried (Na2SO4), then the solvent removed under reduced pressure to afford a pale yellow solid which was purified by chromatography on silica gel (50% EtOAc/PE as eluant) to afford 2-(4-allyl-2-fluoroanilino)-3,4-difluorobenzoic acid as pale yellow needles (583 mg, 72%); m.p. (EtOAc/hexane) 199-201° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.68 (v br s, 1 H), 9.25 (br s, 1 H), 7.81 (ddd, J=8.3, 6.1, 2.0 Hz, 1 H), 7.07 (dd, J=12.2, 1.7 Hz, 1 H), 7.06-6.98 (m, 2 H), 6.93 (dd, J=8.2, 1.6 Hz, 1 H), 6.01-5.89 (m, 1 H), 5.13-5.03 (m, 2 H), 3.51-3.40 (m, 2H, obscured by H2O). Anal. calcd. for C16H12F3NO2: C, 62.5; H, 3.9; N, 4.6. Found C, 62.7; H, 4.1; N, 4.5.

Provenance & Evidence