反应详情

Hydroxylamine, hydrochloride (0.0131 mol) was added to a solution of (±)-4-[[4-(3-chlorophenyl)-1,2-dihydro-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehyde monohydrochloride (described in Example B1) (0.0087 mol) in ethanol (45 ml). The mixture was stirred at room temperature for 1 hour and 30 minutes then refluxed for 2 hours, poured out into K2CO3 10% and extracted with EtOAc. The organic layer was separated, dried MgSO4), filtered and the solvent was evaporated. The residue (4.86 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.1; 15–40 μm). The pure fractions were collected and the solvent was evaporated, yielding: two fractions. The first fraction was crystallized from CH3CN/diethyl ether. The precipitate was filtered off and dried, yielding 1.69 g (38%) of -4-[[4-(3-chlorophenyl)-1,2-dihydro-2-oxo-6-quinolinyl]ethoxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehyde oxime, of indeterminate E/Z configuration mp. 232° C. The second fraction was crystallized from CH3CN/diethyl ether. The precipitate was filtered off and dried, yielding 1.91 g (45%) of -4-[[4-(3-chlorophenyl)-1,2-dihydro-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehyde oxime, of indeterminate E/Z configuration, mp. 230° C.

1. temperaturethen refluxed for 2 hours
2. extractionextracted with EtOAc
3. customThe organic layer was separated
4. filtrationdried MgSO4), filtered
5. customthe solvent was evaporated
6. customThe residue (4.86 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.1; 15–40 μm)
7. customThe pure fractions were collected
8. customthe solvent was evaporated
9. customyielding
10. customThe first fraction was crystallized from CH3CN/diethyl ether
11. filtrationThe precipitate was filtered off
12. customdried