Acetonitrile → 4-Chloro-7-fluoro-3-methyl-2-(2-(methylthio)phenyl)quinoline

HRID 1618541Notes

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.[CH3:15][S:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>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].O>[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:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[S:16][CH3:15])[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2,4-dichloro-7-fluoro-3-methylquinoline (100 mg, 0.44 mmol), 2-(methylthio)phenylboronic acid (95 mg, 0.57 mmol) (in a mixture with the 5-F regioisomer; described herein), tetrakis(triphenylphosphine)palladium(o) (25.1 mg, 0.022 mmol), sodium carbonate (230 mg, 2.17 mmol), acetonitrile (3 mL), and water (1.5 mL) was heated in a microwave at 100° C. for 60 min, then partitioned between EtOAc and water. The organic layer was washed with brine, dried (MgSO4), and concentrated. Column chromatography afforded (in order of elution) 4-chloro-7-fluoro-3-methyl-2-(2-(methylthio)phenyl)quinoline and 4-chloro-5-fluoro-3-methyl-2-(2-(methylthio)phenyl) as white solids. Mass Spectrum (ESI) m/e=318 (M+1).

Workup

custompartitioned between EtOAc and water
washThe organic layer was washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-963a6ef740ea4539a93ada5633e366ff
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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