4-Bromoanisole → 4-(4-Methoxyphenyl)pyridine

HRID 2288690Notes

Reaction equation

HRID 2288690 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.BrC1C=CC(OC)=CC=1.[Mg].Cl.Br[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1>O1CCCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Cl-].[Ni+2].C(OC)(C)(C)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 77304-BromoanisoleHCID 881004-Bromopyridinium chlorideHCID 5462224MagnesiumHCID 178491912HCID 178491912, compound

Product 1

HCID 6038134-(4-Methoxyphenyl)pyridine

Reagents, catalysts & solvents 3

HCID 84306Bis(triphenylphosphine)nickel(II)chlorideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of 4-methoxyphenylmagnesium bromide, prepared from 4-bromoanisole (150 g 0.80 mol) and magnesium (20 g, 0.83 mol) in dry tetrahydrofuran (300 mL) is filtered, cooled to -10° C. and added cautiously to a stirred mixture of bis-(triphenylphosphine)nickel (II) chloride (1.5 g, 2.25 mmol) and 4-bromopyridine hydrochloride (65 g, 0.334 mol) in dry tetrahydrofuran (300 mL) at 10° C. under an argon atmosphere. After 50% of the Grignard reagent had been added a vigorous, exothermic reaction sets in and the temperature of the mixture is maintained between 50 and 60° C. throughout the rest of the addition by employing an ice-methanol cooling bath. When the addition is complete the mixture is stirred for 60 min at 50° C. The solvent is evaporated off under reduced pressure to yield a residue which is treated with t-butylmethylether (500 mL) and extracted with hydrochloric acid (3×300 mL of 5M). The combined extracts are washed (t-butylmethylether), basified (aqueous NaOH) and extracted with

Workup

  1. filtrationis filtered
  2. customexothermic reaction sets in and the temperature of the mixture
  3. temperatureis maintained between 50 and 60° C. throughout the rest of the addition
  4. additionWhen the addition
  5. customThe solvent is evaporated off under reduced pressure
  6. customto yield a residue which
  7. extractionextracted with hydrochloric acid (3×300 mL of 5M)
  8. washThe combined extracts are washed (t-butylmethylether)
  9. extractionextracted with

Sources & evidence

ORD record
ord-779483bdde874a0a8f42ecd2710f40ed
Source dataset
uspto-grants-2000_07
Patent number
US06090817

Reaction notes

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