2-Chloro-3-methylpyridine → 3-Methyl-2-(4-(trifluoromethyl)phenyl)pyridine

HRID 1869737Notes

Reaction equation

HRID 1869737 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1>COCCOC.C([O-])([O-])=O.[Na+].[Na+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:8][C:7]1[C:2]([C:14]2[CH:15]=[CH:16][C:11]([C:10]([F:21])([F:20])[F:9])=[CH:12][CH:13]=2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 876032-Chloro-3-methylpyridineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 167414253-Methyl-2-(4-(trifluoromethyl)phenyl)pyridine

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of 2-chloro-3-methylpyridine (6.38 g, 50 mmol) and 4-(trifluoromethyl)benzeneboronic acid (9.59 g, 50 mmol) in DME (75 ml) and Na2CO3 solution (2M, 75 ml) was deoxygenated by bubbling nitrogen through the mixture for 15 mins. Tetrakis (triphenylphosphine) palladium (0) (1.155 g, 1.0 mmol) was added and the reaction was degassed for a further 10 mins. The reaction was heated at reflux for 16 hrs then cooled to rt. The mixture was extracted with EtOAc (×3), the combined extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by chromatography (silica, 10-30% EtOAc/isohexane) to give the pyridine (10.75 g, 91%). 1H NMR (360 MHz, CDCl3) δ: 2.36 (3H, s), 7.21-7.26 (1H, m), 7.60-7.72 (5H, m), 8.54-8.55 (1H, m).

Workup

  1. customwas deoxygenated
  2. customby bubbling nitrogen through the mixture for 15 mins
  3. customthe reaction was degassed for a further 10 mins
  4. temperatureThe reaction was heated
  5. temperatureat reflux for 16 hrs
  6. extractionThe mixture was extracted with EtOAc (×3)
  7. washthe combined extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by chromatography (silica, 10-30% EtOAc/isohexane)
  12. customto give the pyridine (10.75 g, 91%)

Sources & evidence

ORD record
ord-4abc22e00e874757b5600b721a594e60
Source dataset
uspto-grants-2009_12
Patent number
US07638629B2

Reaction notes

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