Diphenyl Ether → Ethyl 5,7-dichloro-4-oxo-1,4-dihydroquinoline-2-carboxylate
Reaction equation
[C:1]1(OC2C=CC=CC=2)C=CC=C[CH:2]=1.C([C:16]1[C:21]([NH:22]/[C:23](=[CH:27]\[C:28]([O-:30])=O)/[C:24]([O-:26])=[O:25])=[C:20](CC)[C:19]([Cl:33])=[CH:18][C:17]=1[Cl:34])C>>[Cl:33][C:19]1[CH:18]=[C:17]([Cl:34])[CH:16]=[C:21]2[C:20]=1[C:28](=[O:30])[CH:27]=[C:23]([C:24]([O:26][CH2:1][CH3:2])=[O:25])[NH:22]2Participants
Conditions
- Temperature
- 244 °C
Procedure
A 5-L three-neck flask equipped with a thermocouple, an addition funnel, and a distillation apparatus was charged with diphenyl ether (about 2.8 L), which was heated to about 244° C. The concentrated reaction mixture containing Compound 3 (about 1.1 mole) from Reaction 1, above, was added from the dropping funnel into the hot diphenyl ether over about 10 minutes with a nitrogen purge. The funnel was rinsed with about 200 mL of diphenyl ether, which was also added to the flask. The resulting mixture was heated at about 244° C. for about 1 hour to cyclize Compound 3 to form Compound 4. The reaction mixture then was cooled to room temperature, at which point Compound 4 crystallized out. The crystallized product was isolated and slurried with ethyl acetate (EtOAc; about 1 L). The crystals were collected and rinsed with EtOAc (3×500 mL), and then dried under high vacuum at room temperature to afford about 269.95 g of Compound 4 (85.8% yield over two steps).
Workup
- customA 5-L three-neck flask equipped with a thermocouple, an addition funnel
- customThe concentrated reaction mixture
- customfrom Reaction 1
- custompurge
- washThe funnel was rinsed with about 200 mL of diphenyl ether, which
- additionwas also added to the flask
- temperatureThe resulting mixture was heated at about 244° C. for about 1 hour
Sources & evidence
- ORD record
- ord-0e9d5a24949b494a9b6caa6af51e9f84
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07923458B2
Reaction notes
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