Ammonium Hydroxide → 2-(3-Trifluoromethoxyphenyl)-5-methylpyridine

HRID 363190Notes

Reaction equation

HRID 363190 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:6][CH:7]=1.C([Li])(C)(C)C.Br[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=1.[OH-].[NH4+]>C1COCC1.CCCCC.C(OCC)C.[Cl-].[Zn+2].[Cl-].[Ni].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>[F:10][C:9]([F:12])([F:11])[O:8][C:4]1[CH:3]=[C:2]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=2)[CH:7]=[CH:6][CH:5]=1

Participants

10

Reactant 4

HCID 14923Ammonium HydroxideHCID 5199641-Bromo-3-(trifluoromethoxy)benzeneHCID 5642162-Bromo-5-methylpyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 545201462-(3-Trifluoromethoxyphenyl)-5-methylpyridine

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 57357981Nickel--triphenylphosphane (1/2)CatalystHCID 3283Diethyl EtherSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-bromotrifluoromethoxybenzene (0.590 mL, 4.00 mmol) in THF (12 mL) at -78° C. was added t-butyl lithium (4.71 mL, of a 1.7M solution in pentane, 8.00 mmol. After 10 minutes zinc chloride(4.0 mL, of a 1M solution in diethylether, 4.00 mmol) was added. The reaction was stirred for 10 minutes at -78° C. and then allowed to warm to 0° C. and stirred for 30 minutes. This solution was added via cannula to a solution of 2-bromo-5-methyl pyridine and bis(triphenylphosphine) Nickel II chloride. The reaction stirred for 1 hour at 0° C. and then at ambient temperature for a furthur 1 hour. Saturated ammonium hydroxide solution (3 mL) was added and the mixture stirred until homogenous, extracted with Et2O and the organic extracts washed with saturated brine, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed (Silica gel, 25-50% CH2Cl2 in hexanes).

Workup

  1. temperatureto warm to 0° C.
  2. stirringstirred for 30 minutes
  3. stirringThe reaction stirred for 1 hour at 0° C.
  4. waitat ambient temperature for a furthur 1 hour
  5. stirringthe mixture stirred until homogenous,
  6. extractionextracted with Et2O
  7. washthe organic extracts washed with saturated brine
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customThe residue was chromatographed (Silica gel, 25-50% CH2Cl2 in hexanes)

Sources & evidence

ORD record
ord-89439644dad44269915f26bafa0e3617
Source dataset
uspto-grants-1999_02
Patent number
US05872136

Reaction notes

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