Iodoethane → 2-Fluoro-4-ethylthioaniline

Participants

Reaction Conditions

Reaction Steps

A solution of the product of Example 26, Step A, 4-amino-3-fluorophenyl thiocyanate (500 mg, 2.97 mmol), in ethanol (7 mL) was added dropwise to a solution of Na2S.9H2O (714 mg, 2.97 mmol) in water (1.5 mL) and the resulting mixture stirred at 50° C. for 1 hour. A solution of ethyl iodide (510 mg, 3.27 mmol) in ethanol (1 mL) was then added and the reaction stirred at 50° C. for a further 6 hours. The mixture was diluted with water (30 mL) and extracted with Et2O (4×10 mL), then the combined Et2O extracts washed with water (3×20 mL), saturated NaCl (20 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure afforded a pale yellow oil which was purified by dry flash column chromatography on silica (5% Et2O/hexanes as eluant) to afford 2-fluoro-4-ethylthioaniline as a colourless oil (470 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 7.08 (dd, J=11.3, 2.0 Hz, 1 H), 7.01 (ddd, J=8.2, 2.0, 0.9 Hz, 1 H), 6.71 (dd, J=9.3, 8.2 Hz, 1 H), 3.81 (br s, 2 H), 2.80 (q, J=7.3 Hz, 2 H), 1.24 (t, J=7.3 Hz, 3 H). Step B: Preparation of 3,4-difluoro-2-[[2-fluoro-4-(ethylthio)phenyl]amino]-benzoic acid

Provenance & Evidence