Cesium fluoride → 2-(2-Fluoro-5-trifluoromethyl-phenyl)-4-methyl-pyridine

HRID 749042Notes

Reaction equation

HRID 749042 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1B(O)O.Cl[C:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][N:17]=1.C(P(C(C)(C)C)C[Si](C)(C)C)(C)(C)C.[F-].[Cs+]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][N:17]=1

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 772482-Chloro-4-methylpyridineHCID 27633012-Fluoro-5-(trifluoromethyl)phenylboronic acidHCID 12583313Di-tert-butyl-trimethylsilylmethyl-phosphane

Product 1

HCID 586112952-(2-Fluoro-5-trifluoromethyl-phenyl)-4-methyl-pyridine

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

10.0 g (0.0481 mol) of 2-fluoro-5-(trifluoromethyl)phenylboronic acid, 5.52 g (0.0433 mol) of 2-chloro-4-methyl-pyridine, 1.10 g (0.0012 mol) of tris(dibenzylideneacetone) dipalladium (0), 0.67 g (0.00289 mol) of di-tert-butyl-trimethylsilylmethyl-phosphane, 8.0 g (0.0527 mol) of cesium fluoride and 100 ml of dioxane were stirred at room temperature for 24 hours. The resultant mixture was poured into 200 ml of water and extracted twice with 200 ml of methylene chloride. The organic phase was dried on magnesium sulfate overnight and filtered. The solvent was removed on a rotovapor and the residue was purified by chromatography on silica gel with petroleum ether/ethyl ether (10/0.5) as eluent. Yield of 2-(2-fluoro-5-trifluoromethyl-phenyl)-4-methyl-pyridine: 4.70 g (42.57%) as a colorless liquid. 1H NMR (CD2Cl2) 2.30 (s, 3H, Me), 6.90-8.50 (m, 6H, arom-H). 19F NMR (CD2Cl2) −63.75 (s, 3F, CF3), −112.44 (s, 1F, F-arom). LC/MS calculated for C13H9F4N 255.07; found 255.07.

Workup

  1. extractionextracted twice with 200 ml of methylene chloride
  2. customThe organic phase was dried on magnesium sulfate overnight
  3. filtrationfiltered
  4. customThe solvent was removed on a rotovapor
  5. customthe residue was purified by chromatography on silica gel with petroleum ether/ethyl ether (10/0.5) as eluent

Sources & evidence

ORD record
ord-a75ef1083b1849dd8e24a4ef9f0fab35
Source dataset
uspto-grants-2008_07
Patent number
US07402345B2

Reaction notes

Loading…