2-Bromo-4-methylpyridine → 4-Methyl-2-pentylpyridine

HRID 241480Notes

Reaction equation

HRID 241480 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[CH2:9]([Mg]Br)[CH2:10][CH2:11][CH2:12][CH3:13]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1>[CH3:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH:7]=1

Participants

5

Reactant 2

HCID 27340872-Bromo-4-methylpyridineHCID 178445865HCID 178445865, compound

Product 1

HCID 30200104-Methyl-2-pentylpyridineYield 44.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A 50 ml reactor under argon was charged with 2-bromo-4-methylpyridine and THF. The reaction was cooled to −78° C. and the Pd(dppf)2Cl2 (dppf being 1,1′-di(diphenylphosphine)-ferrocene) catalyst was added, followed by 3.0 M pentyl magnesium bromide. The reaction was allowed to warm to 0° C. until the starting material was consumed. The reaction was quenched with 20 ml of saturated ammonium chloride solution and extracted with 20 ml of ethylacetate. The ethyl acetate layer was extracted with 20 ml of 1 M aqueous hydrochloric acid to extract the pyridine product from neutral organics. The aqueous acid layer was neutralized with 1 M NaOH and extracted with 20 ml of ethyl acetate. The ethyl acetate layer was washed with brine and dried on anhydrous sodium sulphate. The product phase was filtered and concentrated on the rotary evaporator to give 850 mg of product, a 44.9% yield.

Workup

  1. temperatureto warm to 0° C. until the starting material
  2. customwas consumed
  3. customThe reaction was quenched with 20 ml of saturated ammonium chloride solution
  4. extractionextracted with 20 ml of ethylacetate
  5. extractionThe ethyl acetate layer was extracted with 20 ml of 1 M aqueous hydrochloric acid
  6. extractionto extract the pyridine product from neutral organics
  7. extractionextracted with 20 ml of ethyl acetate
  8. washThe ethyl acetate layer was washed with brine
  9. dry with materialdried on anhydrous sodium sulphate
  10. filtrationThe product phase was filtered
  11. concentrationconcentrated on the rotary evaporator

Sources & evidence

ORD record
ord-1d8638c18a8549c4b8209d8c097b064b
Source dataset
uspto-grants-2014_02
Patent number
US08652452B2

Reaction notes

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