反应详情

温度

50 °C

8.0 g (58.3 mmol) of 2-cyano-3-fluorophenol are dissolved in 100 ml of anhydrous toluene. With exclusion of moisture and under protective argon gas, a solution of 8.489 g (60 mmol) of chlorosulphonyl isocyanate is added dropwise, in the course of which slight exothermicity occurs. The mixture is stirred at 50° C. for 16 hours; phenol is no longer detectable by thin-layer chromatography. The mixture is heated under reflux for 16 hours; no further evolution of HCl gas takes place. The mixture is concentrated under reduced pressure, taken up in acetonitrile and admixed with aqueous acetonitrile. After stirring at room temperature for 1 hour, the mixture is concentrated, and the residue is dissolved in dichloromethane and washed with water. After drying and concentrating the organic phase, 13 g of a reaction mixture are obtained, which is chromatographed on silica gel (450 g, 40-63 μm) with dichloromethane/methanol=99/1. 1.3 g of a fraction are isolated, which consists of two components at log P=0.76 and 1.06. After separating this mixture by means of HPLC, 0.8 g of 4-amino-5-fluoro-1,2,3-benzoxathiazine 2,2-dioxide is obtained as a white solid.

1. temperatureThe mixture is heated
2. temperatureunder reflux for 16 hours
3. concentrationThe mixture is concentrated under reduced pressure
4. stirringAfter stirring at room temperature for 1 hour
5. concentrationthe mixture is concentrated
6. dissolutionthe residue is dissolved in dichloromethane
7. washwashed with water
8. customAfter drying
9. concentrationconcentrating the organic phase, 13 g of a reaction mixture
10. customare obtained
11. customwhich is chromatographed on silica gel (450 g, 40-63 μm) with dichloromethane/methanol=99/1
12. custom1.3 g of a fraction are isolated
13. customAfter separating this mixture by means of HPLC