1,3-Cyclohexanedione → 2-Methyl-4-(3-chloro-4-fluorophenyl)-4,6,7,8-tetrahydro-5(1H)-quinolone

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Reaction Conditions

Reaction Steps

A mixture of 3-chloro-4-fluoro benzaldehyde (2.7 g), 1,3-cyclohexanedione (1.99 g) and 47 mL of ethanol were heated at 50° C. overnight and then cooled to room temperature. Acetone (1.18 g), ammonium acetate (1.97 g) and a premixed solution of pyrrolidine acetate (20.4 mmole) in 5 mL of ethanol were added and heated at 70° C. for three hours and then cooled to room temperature. The solvent was evaporated in vacuo and the residue was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography (eluant: ether/hexane; 9.0/1.0) over silica gel provided the title compound 0.140 g as a yellow solid, m.p. 164°-167° C. 1H-NMR(300MHz, d6-DMSO): 1.74(s,3H,CH3), 1.81-1.88(m,2H, CH2) 2.15-2.19(m,2H, CH2), 2.41-2.48(m,2H,CH2), 4.41(d, 1H, J=4.8 Hz, CH), 4.60(d,1H, J=4.8(Hz,CH), 7.10-7.28(m,3H, aromatic), 8.54(s,1H, NH); MS (Cl , CH4): 292 (M+1): Analysis for C16H15ClFNO: Calculated: C; 65.87; H; 5.18; N; 4.80: Found: C; 65.67; H; 5.50; N; 4.48.

Provenance & Evidence