Hydrochloric Acid → 1-(4-Fluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid ethyl ester
Reaction equation
[C:1]([O:9]CC)(=O)[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[H][H].[F:16][C:17]1[CH:35]=[CH:34][C:20]([CH2:21][N:22]2[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[C:25](=O)[O:24]C2=O)=[CH:19][CH:18]=1.Cl>CC(N(C)C)=O>[CH2:6]([O:5][C:3]([C:2]1[C:1](=[O:9])[N:22]([CH2:21][C:20]2[CH:19]=[CH:18][C:17]([F:16])=[CH:35][CH:34]=2)[C:27]2[C:26]([C:25]=1[OH:24])=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:4])[CH3:7]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
A solution of diethyl malonate (8.0 g, 51 mmol) was added slowly to a suspension of sodium hydride (60% in mineral oil, 2.21 g, 55 mmol) in dimethylacetamide under N2 atmosphere. The mixture was stirred at room temperature until the evolution of hydrogen gas ceased, then heated to 90° C. for 30 min. and cooled to room temperature. A solution of Compound 5 (15 g, 53 mmol) in dimethylacetamide was added slowly to the mixture, which was heated overnight at 120° C. The mixture was cooled to room temperature, poured into ice water, and acidified by cold 10% HCl. The solids formed were filtered and washed several times by water to yield 13.37 g (78%) of white solids. M.P. 116-120° C. 1H NMR (DMSO-d6): δ 1.31 (t, J=7.0 Hz, 3H), 4.36 (q, J=7.0 Hz, 2H), 5.43 (s, 2H), 7.13 (m, 2H), 7.23-7.30 (m, 3H), 7.37 (d, J=8.5 Hz, 1H), 7.63 (t, J=7.0 Hz, 1H), 8.08 (d, J=7.6 Hz, 1H), 13.20 (s, 1H). EIMS m/z 342 (M+1), 364 (M+23). Anal. (C19H16FNO4) C, H, N.
Workup
- temperaturecooled to room temperature
- temperaturewas heated overnight at 120° C
- temperatureThe mixture was cooled to room temperature
- customThe solids formed
- filtrationwere filtered
- washwashed several times by water
Sources & evidence
- ORD record
- ord-99dedbda881449428e61cebdaf5a94f7
- Source dataset
- uspto-grants-2007_12
- Patent number
- US07312221B2
Reaction notes
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