反应详情

To a mixture of 2-amino-4,5-difluoro-1,3-benzothiazole (130 mg, 0.70 mmol) and CuSO4 (20 mg) in conc. HCl (20 mL) was added NaNO2 (96 mg, 1.4 mmol, 2 eq, dissolved in 5 mL of water) dropwise at −10° C. over about 15 min. The reaction mixture was stirred for 1 h, poured into a solution of CuCl (67 mg, 0.7 mmol, 1 eq.) in conc. HCl (20 mL), and stirring was continued at ambient temp. for 30 min. The reaction mixture was extracted with diethyl ether (3×30 mL). The combined organic layers were washed with water (10 mL), dilute ammonium hydroxide (10 mL), brine (20 ml), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluted by 2% methanol in methylene chloride) to afford the title compound. 1H-NMR (CDCl3, 300 MHz): δ=7.20-7.15 (m, 1H), 7.13-7.04 (m, 1H).

1. stirringstirring
2. waitwas continued at ambient temp. for 30 min
3. extractionThe reaction mixture was extracted with diethyl ether (3×30 mL)
4. washThe combined organic layers were washed with water (10 mL), dilute ammonium hydroxide (10 mL), brine (20 ml)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by column chromatography on silica gel (eluted by 2% methanol in methylene chloride)