[Cl:1][CH2:2][C@H:3]1[CH2:7]OS(=O)(=O)[O:4]1.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C:18]2=[O:23])=[CH:13][CH:12]=1.C(N(CC)CC)C.CS(O)(=O)=O.O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[Cl:1][CH2:2][C@H:3]([OH:4])[CH2:7][NH:10][C:11]1[CH:12]=[CH:13][C:14]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C:18]2=[O:23])=[CH:15][CH:16]=1Under 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%.
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