Sodium Carbonate → 4-Chloro-2-(2,5-difluorophenyl)-7-fluoro-3-methylquinoline

HRID 1618562Notes

Reaction equation

Cl[C:2]1[C:11]([CH3:12])=[C:10]([Cl:13])[C:9]2[C:4](=[CH:5][C:6]([F:14])=[CH:7][CH:8]=2)[N:3]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[Cl:13][C:10]1[C:9]2[C:4](=[CH:5][C:6]([F:14])=[CH:7][CH:8]=2)[N:3]=[C:2]([C:20]2[CH:21]=[C:16]([F:15])[CH:17]=[CH:18][C:19]=2[F:22])[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 2,4-dichloro-7-fluoro-3-methylquinoline (300 mg, 1.30 mmol) (in a mixture with the 5-F regioisomer; described herein), 2,5-difluorophenylboronic acid (268 mg, 1.70 mmol), tetrakis(triphenylphosphine)palladium(o) (151 mg, 0.130 mmol), and sodium carbonate (69 mg, 6.52 mmol) in acetonitrile (9.7 mL) and water (4.9 mL) was stirred and heated in a microwave at 100° C. for 120 min. The reaction mixture was then partitioned between EtOAc and water, and the organic layer was washed with brine, dried (MgSO4), and concentrated. Column chromatography of the crude product afforded 4-chloro-2-(2,5-difluorophenyl)-7-fluoro-3-methylquinoline) as a white solid. Mass Spectrum (ESI) m/e=308 (M+1).

Workup

customThe reaction mixture was then partitioned between EtOAc and water
washthe organic layer was washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-036ae1406d3b499fa88503c08e36b465
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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