Cesium carbonate → 2-[2-Fluoro-5-(trifluoromethyl)phenyl]-4-nitropyridine

HRID 749043Notes

Reaction equation

HRID 749043 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]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][N:17]=1.C(P(C(C)(C)C)C[Si](C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[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]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][N:17]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 7351522-Chloro-4-nitropyridineHCID 27633012-Fluoro-5-(trifluoromethyl)phenylboronic acidHCID 12583313Di-tert-butyl-trimethylsilylmethyl-phosphane

Product 1

HCID 586112932-[2-Fluoro-5-(trifluoromethyl)phenyl]-4-nitropyridine

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, 6.86 g (0.0433 mol) of 2-chloro-4-nitro-pyridine, 1.10 g (0.0012 mol) of tris(dibenzylideneacetone) dipalladium (0), 0.67 g (0.00289 mol) of di-tert-butyl-trimethylsilylmethyl-phosphane, 15.67 g (0.0481 mol) of cesium carbonate 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 over 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-nitro-pyridine: 3.58 g (28.92%) as a white solid with m.p. 58.11° C. 1H NMR (CD2Cl2) 7.10-8.90 (m, 6H, arom-H). 19F NMR (CD2Cl2) −62.98 (s, 3F, CF3), −111.85 (s,1F, F-arom). LC/MS calculated for C12H6F4N2O2 286.04; found 286.04.

Workup

  1. extractionextracted twice with 200 ml of methylene chloride
  2. dry with materialThe organic phase was dried over 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-aa169f7d5d3f44878f214e2be44a1fb1
Source dataset
uspto-grants-2008_07
Patent number
US07402345B2

Reaction notes

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