2-Chloro-4-(4-methoxyphenyl)pyridine → 4-(4-Methoxyphenyl)-2-methylpyridine

HRID 657662Notes

Reaction equation

HRID 657662 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[CH3:16][Mg]Br>O1CCCC1>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:16])[CH:7]=2)=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 534408782-Chloro-4-(4-methoxyphenyl)pyridineHCID 178418573HCID 178418573, compound

Product 1

HCID 233717804-(4-Methoxyphenyl)-2-methylpyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 2-chloro-4-(4-methoxyphenyl)pyridine (660 mg) and bis(triphenyl-phosphine)nickeldichloride (200 mg) in anhydrous tetrahydrofuran (7.5 mL) is cooled to a temperature close to 0° C. A solution of methylmagnesiumbromide in tetrahydrofuran (2.6 M, 2 mL) is added slowly. The mixture is stirred at room temperature for two hours, concentrated under reduced pressure and dissolved in methyl tert-butyl ether (10 mL). Alkaloids are extracted with a 3N aqueous solution of hydrochloric acid (3 times 10 mL). Extracts are pooled, alkalinised and back extracted with methyl tert-butyl ether (3 times 20 mL) and dichloromethane (30 mL). Organic phases are dried over magnesium sulphate, concentrated under reduced pressure and purified over silica gel (eluent dichloromethane/methanol from 100/0 to 95/5). Fraction containing the expected product are pooled and concentrated under reduced pressure to give 385 mg of 4-(4-methoxyphenyl)-2-methylpyridine as a clear brown powder used without further purification.

Workup

  1. temperatureis cooled to a temperature
  2. customclose to 0° C
  3. concentrationconcentrated under reduced pressure
  4. dissolutiondissolved in methyl tert-butyl ether (10 mL)
  5. extractionAlkaloids are extracted with a 3N aqueous solution of hydrochloric acid (3 times 10 mL)
  6. extractionback extracted with methyl tert-butyl ether (3 times 20 mL) and dichloromethane (30 mL)
  7. dry with materialOrganic phases are dried over magnesium sulphate
  8. concentrationconcentrated under reduced pressure
  9. custompurified over silica gel (eluent dichloromethane/methanol from 100/0 to 95/5)
  10. additionFraction containing the expected product
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-305abb4e9af24ae1bb743ac7acdfa6c5
Source dataset
uspto-grants-2011_12
Patent number
US08076329B2

Reaction notes

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