Toluene → 4-Chloro-5,7-difluoro-3-methyl-2-(naphthalen-1-yl)quinoline

HRID 1618656Notes

Reaction equation

Cl[C:2]1[C:11]([CH3:12])=[C:10]([Cl:13])[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=1.[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:13][C:10]1[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=[C:2]([C:24]2[C:25]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:21]=[CH:22][CH:23]=2)[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 100 °C

Procedure

A microwave vessel was charged with 2,4-dichloro-5,7-difluoro-3-methylquinoline (250 mg, 1.008 mmol), 2-naphthylboronic acid (225 mg, 1.310 mmol), tetrakis(triphenylphosphine)palladium(0) (87 mg, 0.076 mmol), sodium carbonate (534 mg, 5.04 mmol), toluene (8.06 mL), and water (2.02 mL). The mixture was heated at 100° C. for 2 h, then cooled to rt and partitioned between EtOAc and water. The organic layer was washed with brine, dried (MgSO4), and concentrated. The resulting crude material was purified by flash chromatography, eluting with a gradient of 0-6% EtOAc in hexane to give 4-chloro-5,7-difluoro-3-methyl-2-(naphthalen-1-yl)quinoline. Mass Spectrum (ESI) m/e=340.0 (M+1).

Workup

temperaturecooled to rt
custompartitioned between EtOAc and water
washThe organic layer was washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe resulting crude material was purified by flash chromatography
washeluting with a gradient of 0-6% EtOAc in hexane

Sources & evidence

ORD record: ord-f1e8c2adad5d4874ab91156b28edb5c6
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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