Benzene, 1-bromo-4-(trifluoromethyl)- → 4-Methyl-2,3,5-trifluoro-6-(4-trifluoromethylphenyl)pyridine

HRID 382239Notes

Reaction equation

HRID 382239 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1.[CH3:17][C:18]1[C:23]([F:24])=[C:22](F)[N:21]=[C:20]([F:26])[C:19]=1[F:27]>C(OCC)C>[CH3:17][C:18]1[C:23]([F:24])=[C:22]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[N:21]=[C:20]([F:26])[C:19]=1[F:27]

Participants

5

Reactant 3

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 46613162,3,5,6-Tetrafluoro-4-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 114377574-Methyl-2,3,5-trifluoro-6-(4-trifluoromethylphenyl)pyridineYield 25.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
10 °C

Procedure

Butyl lithium (2.7 ml, 6.7 mmol, 2.5 M solution in hexane) is added to a solution of 1-bromo-4-trifluoromethyl benzene (1.0 ml, 7.3 mmol) in anhydrous diethyl ether (10 ml) at −20° C. The mixture is stirred for 60 min at −20° C. and for 60 min at 10° C. After cooling to −40° C. 4-methyl-2,3,5,6-tetrafluoropyridine (1.1 g, 6.6 mmol) is added. The resulting mixture is stirred for 120 min at −30° C. and then is allowed to warm to ambient temperature. After 2 days at ambient temperature the mixture is washed twice with saturated aqueous ammonium chloride. The layers are separated and the organic layer is dried with anhydrous magnesium sulfate and filtered. After removal of the solvents in vacuo, the crude product is purified by flash column chromatography (silica gel, pentane/ethyl acetate=9/1 by volume) yielding colorless crystals of 4-methyl-2,3,5-trifluoro-6-(4-trifluoromethylphenyl)pyridine (0.5 g, 1.7 mmol) of mp. 52° C.

Workup

  1. temperatureAfter cooling to −40° C
  2. stirringThe resulting mixture is stirred for 120 min at −30° C.
  3. temperatureto warm to ambient temperature
  4. washAfter 2 days at ambient temperature the mixture is washed twice with saturated aqueous ammonium chloride
  5. customThe layers are separated
  6. dry with materialthe organic layer is dried with anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customAfter removal of the solvents in vacuo
  9. customthe crude product is purified by flash column chromatography (silica gel, pentane/ethyl acetate=9/1 by volume)

Sources & evidence

ORD record
ord-ee171283d4294b6ba526a0a7e0010c8b
Source dataset
uspto-grants-2001_10
Patent number
US06310006B1

Reaction notes

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