反应详情

Under an atmosphere of nitrogen to a solution of a 14.22 g of (R)-4-chloromethyl-[1,3,2]dioxathiolane 2,2-dioxide (MW=156.59; 1.37 eq.) in 190 mL of methylenechloride were added 12.68 g of 4-(4-amino-phenyl)-morpholin-3-one (APMO) (MW=192.22; 1 eq.) and 9.2 g (MW=101.12; 1.37 eq.) of triethylamine. The reaction mixture was stirred for 24 h at room temperature. Then the resulting suspension was concentrated in vacuo and the concentrate was dissolved in 400 mL of acetonitrile. 38 g of methane sulfonic acid (MW=96.11; 6.0 eq.). and 7.9 g of water (MW=18.02; 9.0 eq.) were added and the solution were stirred at ambient temperature. After stirring for 5 h, the reaction mixture was neutralized by addition of 50 g of sodium hydrogencarbonate (MW=84.01; 9.0 eq.). The resulting suspension was filtered and the cake washed with 200 mL of acetonitrile. The combined acetonitrile layers were concentrated in vacuo. To the concentrate were added 260 mL of 2-propanol and the mixture was stirred for 1 h at ambient temperature. The resulting slurry was cooled to 0° C. After stirring for at least 2 h at this temperature, the product was isolated by filtration and the filter cake was washed with 50 mL of 2-propanol. After drying in vacuo at 30° C., 11.75 g of the crystalline title compound (MW=284.75) were isolated. Yield=62.6%.

1. concentrationThen the resulting suspension was concentrated in vacuo
2. dissolutionthe concentrate was dissolved in 400 mL of acetonitrile
3. stirringthe solution were stirred at ambient temperature
4. stirringAfter stirring for 5 h
5. filtrationThe resulting suspension was filtered
6. washthe cake washed with 200 mL of acetonitrile
7. concentrationThe combined acetonitrile layers were concentrated in vacuo
8. additionTo the concentrate were added 260 mL of 2-propanol
9. stirringthe mixture was stirred for 1 h at ambient temperature
10. temperatureThe resulting slurry was cooled to 0° C
11. stirringAfter stirring for at least 2 h at this temperature
12. customthe product was isolated by filtration
13. washthe filter cake was washed with 50 mL of 2-propanol
14. customAfter drying in vacuo at 30° C.