反应详情

3-(4-Morpholinyl)propionic acid (0.600 g, 2.11 mmol), prepared by condensation of morpholine with ethyl acrylate (3 equivalents) in refluxing ethanol, followed by distillation, saponification (1N aqueous sodium hydroxide, tetrahydrofuran, reflux), neutralization (1N HCl) and lyophilization, was combined with 1,3-dicyclohexylcarbodiimide (0.434 g, 2.11 mmol), 4-(dimethylamino)pyridine (13 mg, 0.11 mmol), (S)-N-[[3-[3-fluoro-4-(1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (0.354 g, 1.05 mmol), and 1:1 tetrahydrofuran/dichloromethane (50 mL) at room temperature. After 3 days the reaction mixture was filtered to remove the precipitated 1,3-dicyclohexylurea and the filtrate concentrated in vacuo. The crude product was chromatographed over silica gel (20 g), eluting with a gradient of 1-6% methanol/chloroform, to give 0.446 g (95%) of the title compound as a white solid with mp 209°-210° C. ##STR12##

1. distillationfollowed by distillation, saponification (1N aqueous sodium hydroxide, tetrahydrofuran, reflux), neutralization (1N HCl) and lyophilization
2. filtrationAfter 3 days the reaction mixture was filtered
3. customto remove the precipitated 1,3-dicyclohexylurea
4. concentrationthe filtrate concentrated in vacuo
5. customThe crude product was chromatographed over silica gel (20 g)
6. washeluting with a gradient of 1-6% methanol/chloroform