反应详情

3-Cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carbonitrile (3) (6.3 g, 23.5 mmol) is dissolved in conc. sulfuric acid (31.5 mL) and stirred at room temperature for 24 hrs. Ice was added and the resulting suspension was filtered and washed with water and then washed with 1N NaOH. The solids were dried in vacuo to obtain crude 3-cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carboxylic acid amide (4, 8.7 g). This solid is slurried in acetic acid (37 mL) and acetic anhydride (37 mL). Hydrogen peroxide (30%, 18.5 mL) is then added and the reaction is stirred at room temperature for 18 hours. More hydrogen peroxide (30%, 18.5 mL) is then added and the reaction is stirred at room temperature for 3 days. Water is then added and the suspension is filtered and the solids are further dried in vacuo to provide 5 (5.06 g, 62%). 1H NMR (d6 DMSO): δ 7.97 (1H, s), 7.87 (1H, s), 4.14 (2H, d, J=6.0 Hz), 3.54 (3H, s), 1.59–1.78 (6H, m), 1.09–1.25 (3H, m), 0.94–1.03 (2H, m); LRMS (M+): 318.9.

1. additionIce was added
2. filtrationthe resulting suspension was filtered
3. washwashed with water
4. washwashed with 1N NaOH
5. customThe solids were dried in vacuo
6. customto obtain crude 3-cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carboxylic acid amide (4, 8.7 g)
7. stirringthe reaction is stirred at room temperature for 18 hours
8. stirringthe reaction is stirred at room temperature for 3 days
9. filtrationthe suspension is filtered
10. customthe solids are further dried in vacuo