Cesium fluoride → Methyl 3-chloro-4-(2,4-difluorophenyl)quinoline-6-carboxylate

HRID 533398Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[Cl:16].[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1OB(O)O.[F-].[Cs+].O1CCOCC1>[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[Cl:16][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[C:21]1[CH:20]=[CH:19][C:18]([F:17])=[CH:23][C:22]=1[F:24])=[CH:10][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:8][CH:7]=2

Participants

Conditions

Temperature: 100 °C

Procedure

Under argon gas atmosphere, a mixture of methyl 4-bromo-3-chloroquinoline-6-carboxylate (130 mg), 2,4-difluorophenylboric acid (137 mg), a 1,1′-bis(diphenylphosphino)ferrocene palladium (H) dichloride/dichloromethane complex (177 mg), cesium fluoride (197 mg), 1,4-dioxane (8 mL), and water (2 mL) was heated under stirring in an oil bath at 100° C. for one day. The reaction mixture was returned to room temperature, and water was added, and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified under silica gel column chromatography (hexane/ethyl acetate) to obtain methyl 3-chloro-4-(2,4-difluorophenyl)quinoline-6-carboxylate (100 mg).

Workup

customwas returned to room temperature
extractionextracted with ethyl acetate
concentrationThe organic layer was concentrated under reduced pressure
customthe resulting residue was purified under silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record: ord-777a251daad84671af204320cfc450bb
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853242B2

Reaction notes

Loading…