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

HRID 1618562
Notes
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Reaction equation

HRID 1618562 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 596311082,4-Dichloro-7-fluoro-3-methylquinoline

Product 1

HCID 672845754-Chloro-2-(2,5-difluorophenyl)-7-fluoro-3-methylquinoline

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladium
Catalyst
HCID 962WaterSolvent
HCID 6342AcetonitrileSolvent

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

  1. customThe reaction mixture was then partitioned between EtOAc and water
  2. washthe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes