2,4-Dichloro-5,7-difluoro-3-methylquinoline → 4-Chloro-5,7-difluoro-2-(3-fluorobenzyl)-3-methylquinoline

HRID 1618660Notes

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.[Cl-].[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[CH2:21][Zn+]>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.C1COCC1>[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]([CH2:21][C:20]2[CH:23]=[CH:24][CH:25]=[C:18]([F:17])[CH:19]=2)[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 60 °C

Procedure

A screw cap vial was charged with 2,4-dichloro-5,7-difluoro-3-methylquinoline (500 mg, 2.016 mmol), tetrakis(triphenylphosphine)palladium(0) (233 mg, 0.202 mmol), and THF (5.04 mL). The mixture was sparged with N2, then 3-fluoro-benzylzinc chloride (0.5M in THF, 4.23 mL, 2.116 mmol) was added and the reaction stirred at 60° C. for 2 h. The reaction was then partitioned between EtOAc and water, and the organic layer washed with brine, dried (MgSO4), and concentrated. The crude material was purified by flash chromatography, eluting with a gradient of 0-15% EtOAc in hexane to give 4-chloro-5,7-difluoro-2-(3-fluorobenzyl)-3-methylquinoline. Mass Spectrum (ESI) m/e=322.0 (M+1).

Workup

customA screw cap vial
customThe mixture was sparged with N2
customThe reaction was then partitioned between EtOAc and water
washthe organic layer washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe crude material was purified by flash chromatography
washeluting with a gradient of 0-15% EtOAc in hexane

Sources & evidence

ORD record: ord-48e495a0e4d24589b1e8aaa4cbd2755d
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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