4-Chloro-2-fluoroaniline → 4-(4-Chloro-2-fluoroanilino)-7-methoxy-6-methoxycarbonylquinoline

HRID 393662Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>C1(O)CCCCC1>[Cl:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[C:21]([F:26])[CH:20]=1

Participants

Conditions

Temperature: 130 °C

Procedure

4-Chloro-7-methoxy-6-methoxycarbonylquinoline (1.4 g, 5.5 mmol) was dissolved in cyclohexanol (30 ml) and 4-chloro-2-fluoroaniline (0.786 g, 5.8 mmol) was added. The mixture was heated at 130° C. for 1 hour then at 160° C. for 3hours. The solvent was removed by evaporation and the residue was purified by flash chromatography eluting with methylene chloride/ethylacetate (100/0 increasing to 50/50). The solvent was removed by evaporation and the solid was triturated with ether/isohexanes. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-methoxy-6-methoxycarbonylquinoline (570 mg, 28%).

Workup

customThe solvent was removed by evaporation
customthe residue was purified by flash chromatography
washeluting with methylene chloride/ethylacetate (100/0 increasing to 50/50)
customThe solvent was removed by evaporation
customthe solid was triturated with ether/isohexanes
filtrationThe solid was collected by filtration
washwashed with ether
customdried under vacuum

Sources & evidence

ORD record: ord-24838c84634f4bc7be9d6fa2208f39cd
Source dataset: uspto-grants-2004_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06809097B1

Reaction notes

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