Potassium Carbonate → 2-Chloro-4-(3-fluoro-4-methyl-phenyl)-pyridine

HRID 910694Notes

Reaction equation

HRID 910694 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Br)[CH:5]=[CH:4][N:3]=1.C1(C)C=CC=CC=1.CCO.[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][C:25]=1[CH3:26].C([O-])([O-])=O.[K+].[K+]>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:1][C:2]1[CH:7]=[C:6]([C:22]2[CH:23]=[CH:24][C:25]([CH3:26])=[C:20]([F:19])[CH:21]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27826743-Fluoro-4-methylbenzeneboronic acidHCID 38477704-Bromo-2-chloropyridineHCID 21863594Toluene ethanol

Product 1

HCID 866286372-Chloro-4-(3-fluoro-4-methyl-phenyl)-pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a vial was added 2-chloro-4-bromopyridine (96 mg, 0.5 mmol), Pd(PPh3)4 (30 mg), and toluene/EtOH (4:1, 3 mL). After stirring at room temperature for 5 min, 3-fluoro-4-methylphenylboronic acid (115 mg, 0.75 mmol) and 2 M aqueous K2CO3 (1 mL) were added, and the resulting mixture was heated at 90° C. for 16 h. The resulting mixture was poured into water and extracted with EtOAc. The organic layer was dried and concentrated, and the residue was purified by preparative TLC (hexanes/EtOAc) to yield 2-chloro-4-(3-fluoro-4-methyl-phenyl)-pyridine as a solid.

Workup

  1. temperaturethe resulting mixture was heated at 90° C. for 16 h
  2. extractionextracted with EtOAc
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customthe residue was purified by preparative TLC (hexanes/EtOAc)

Sources & evidence

ORD record
ord-5f27c9a387144f5aaf82d164f79b8397
Source dataset
uspto-grants-2011_09
Patent number
US08022209B2

Reaction notes

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