Hydrochloric Acid → Methyl 4-fluoro-5-((2-fluorophenyl)amino)benzo[d][1, 2,3]thiadiazole-6-carboxylate

Participants

Reaction Steps

To a solution of methyl 4-amino-5-(benzylthio)-3-fluoro-2-((2-fluoro-phenyl)amino)benzoate (2.07 g, 5.17 mmol) in acetic acid (60 mL) was added HCl (con., 8 mL) and water (6 mL). The resultant was stirred at ambient temperature for 1 h. A solution of NaNO2 (0.43 g, 6.21 mmol) in water (10 mL) was added dropwisely at 0° C. within 20 min. After stirring for 3 h, the reaction was treated with saturated NaHCO3 (aq.) till the solution was neutral. The aqueous layer was extracted with ethyl acetate (30 mL×3). The combined organic extract was washed with water (30 mL×3) and brine (30 mL) sequentially, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 5:1, v/v) to give the corresponding product (yellow solid, 1.53 g, 92.1% yield). 1H NMR (400 MHz, CDCl3): δ 8.65 (s, 1H), 8.48 (s, 1H), 7.00-6.90 (m, 4H), 3.94 (s, 3H).

Provenance & Evidence