Ammonium Chloride → 2-Benzyl-4-chloro-5,7-difluoro-3-methylquinoline

HRID 1431457Notes

Reaction equation

HRID 1431457 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.[Br-].[CH2:17]([Zn+])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[NH4+]>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>[CH2:17]([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)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 596310402,4-Dichloro-5,7-difluoro-3-methylquinolineHCID 178419772HCID 178419772, compound

Product 1

HCID 596314902-Benzyl-4-chloro-5,7-difluoro-3-methylquinolineYield 51%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A screw cap vial was sequentially charged with 2,4-dichloro-5,7-difluoro-3-methylquinoline (250 mg, 1.00 mmol), tetrakis(triphenylphosphine)palladium(0) (116 mg, 0.10 mmol), and dry THF (2.52 mL). The mixture was then sparged with N2 prior to the addition of benzylzinc(II) bromide (0.5M in THF, 2.12 mL, 1.06 mmol). The reaction was stirred under N2 at 60° C. for 2 h. The reaction was then cooled to rt, slowly poured over satd aq. ammonium chloride and ice, and extracted with EtOAc. The organic layer was washed with water and brine, dried (MgSO4), and concentrated. The crude product then was triturated with toluene, affording 2-benzyl-4-chloro-5,7-difluoro-3-methylquinoline (155 mg, 0.510 mmol). Mass Spectrum (ESI) m/e=304.0 (M+1).

Workup

  1. customA screw cap
  2. customThe mixture was then sparged with N2
  3. temperatureThe reaction was then cooled to rt
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude product then was triturated with toluene

Sources & evidence

ORD record
ord-1fdf05aada1840258588ad4206f2e91a
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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