Toluene → 4-Chloro-2-(3-chlorophenyl)-6-(trifluoromethyl)pyridine

HRID 1508811Notes

Reaction equation

HRID 1508811 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1.[Cl:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>C(OCC)(=O)C.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.CCO>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=[C:2]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:13])[CH:19]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 135768912,4-Dichloro-6-(trifluoromethyl)pyridine

Product 1

HCID 901126574-Chloro-2-(3-chlorophenyl)-6-(trifluoromethyl)pyridineYield 55%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A 500-mL round bottomed flask was charged with 2,4-dichloro-6-trifluoromethylpyridine (2.00 g, 9.26 mmol), (3-chlorophenyl)boronic acid (1.59 g, 10.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.535 g, 0.46 mmol), and Cs2CO3 (9.05 g, 27.8 mmol). Toluene (40 ml), EtOH (10 ml) and water (20 ml) were added. The resulting mixture was stirred under Ar at 90° C. for 4 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL) and hexanes (100 mL). The aqueous layer was separated and the organic layer was washed with saturated sodium chloride (2×25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (100:1 to 95:5) as eluent followed by chromatography on silica using hexane/dichloromethane (100:0 to 80:20) as eluent to afford the title compound (1.48 g, 55%) as a white solid. MW=292.08. 1H NMR (CDCl3, 500 MHz) δ 8.06-8.04 (m, 1H), 7.92 (dt, J=7.0, 2.0 Hz, 1H), 7.89 (d, J=1.5 Hz, 1H), 7.64 (d, J=1.5 Hz, 1H), 7.48-7.42 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe aqueous layer was separated
  3. washthe organic layer was washed with saturated sodium chloride (2×25 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-d1b66728160f42058eeb8658e50a803b
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

Loading…