Ethyl Acetoacetate → 6-chloro-7-methoxy-2-methylquinolin-4(1H)-one
Reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([O:8][CH3:9])[CH:7]=1.[C:11](OCC)(=[O:16])[CH2:12][C:13]([CH3:15])=O>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Cl:10][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][C:6]=1[O:8][CH3:9])[NH:1][C:13]([CH3:15])=[CH:12][C:11]2=[O:16]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
A solution of 5-amino-2-chloroanisole (10.0 g, 63.5 mmol), ethyl acetoacetate (8.1 ml, 63.5 mmol) and catalytic para-toluene sulfonic acid (302 mg, 1.59 mmol) in 65 ml benzene over 4 A molecular sieves was stirred 6 hours at reflux (90° C. external temperature). The reaction mixture was then filtered and concentrated in vacuo. A mixture of the resulting residue and 6.4 ml DOWTHERM A was heated to 250° C. for 20 min. The reaction mixture was cooled to room temperature, and the precipitate was washed with hexanes and ethyl acetate to give 6.43 g (45% yield) of 6-chloro-7-methoxy-2-methylquinolin-4(1H)-one as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ 11.54 (bs, 1H), 7.94 (s, 1H), 7.02 (s, 1H), 5.86 (s, 1H), 3.94 (s, 3H), 2.31 (s, 3H).
Workup
- filtrationThe reaction mixture was then filtered
- concentrationconcentrated in vacuo
- additionA mixture of the resulting residue and 6.4 ml DOWTHERM A
- temperaturewas heated to 250° C. for 20 min
- temperatureThe reaction mixture was cooled to room temperature
- washthe precipitate was washed with hexanes and ethyl acetate
Sources & evidence
- ORD record
- ord-dca8cfc1b3044343a87c39fdce4c8814
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08598354B2
Reaction notes
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