反应详情

30.00 g of 4-[4-((R)-3-chloro-2-hydroxy-propylamino)-phenyl]-morpholin-3-one (MW=284.75; 1 eq.) were added to 1298 g of conc. aqueous ammonia (MW=17.03; 88 eq.). The reaction mixture was stirred for 2.5 h at room temperature. Then 3.0 g of charcoal were added and after 10 min of stirring, the suspension was filtered and the cake was washed with 90 mL of water. Filtrate and wash water were combined and concentrated in vacuo to a mass of 100 g. The concentrate was alkalized by addition of 21.84 g of potassium carbonate (MW=138.21; 1.5 eq.) and to the alkaline solution were added 200 mL of methylenechloride. After 10 min of stirring, the layers were separated and the aqueous layer was extracted once more with 100 mL of methylenechloride. The organic layers were combined and concentrated in vacuo. To the residue were added 150 mL of methyl tert-butyl ether and the resulting suspension was stirred for at least one hour at ambient temperature. Then the crystalline product was isolated by filtration and the filter cake was washed with 75 mL of methyl tert-butyl ether. After drying in vacuo at 30° C., 21.08 g of the crystalline title compound (MW 265.31) were isolated. Yield=75.4%.

1. stirringof stirring
2. filtrationthe suspension was filtered
3. washthe cake was washed with 90 mL of water
4. washFiltrate and wash water
5. concentrationconcentrated in vacuo to a mass of 100 g
6. stirringAfter 10 min of stirring
7. customthe layers were separated
8. extractionthe aqueous layer was extracted once more with 100 mL of methylenechloride
9. concentrationconcentrated in vacuo
10. additionTo the residue were added 150 mL of methyl tert-butyl ether
11. stirringthe resulting suspension was stirred for at least one hour at ambient temperature
12. customThen the crystalline product was isolated by filtration
13. washthe filter cake was washed with 75 mL of methyl tert-butyl ether
14. customAfter drying in vacuo at 30° C.