Diethyl Ether → 4-(Tert-butyl)-2-methylpyridine

HRID 1446717Notes

Reaction equation

HRID 1446717 reaction equation
C[Li].[CH3:3]COCC.[C:8]([C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1)([CH3:11])([CH3:10])[CH3:9]>C(Cl)Cl>[CH3:3][C:14]1[CH:13]=[C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 198784-tert-ButylpyridineHCID 178418348HCID 178418348, compound

Product 1

HCID 132390254-(Tert-butyl)-2-methylpyridineYield 74.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cool a solution of methyl lithium in ether (200 mL, 1.6 M, 320.00 mmol) in an ice bath and add 4-tert-butyl-pyridine (20.28 g, 150.00 mmol) drop wise. Once the substrate is added, warm the reaction to ambient temperature for 3 hours. Concentrate the reaction to near dryness to remove the ether and then add anhydrous toluene (200 mL) and heat to reflux for 20-21 hours. Cool in an ice bath while slowly and cautiously adding ice to quench the reaction. Add water (200 mL) and then extract the aqueous with ethyl acetate (3×250 mL) and separate the layers. Pool, desiccate, filter and concentrate the organic extracts to an oil. Chromatograph the oil on silica using a gradient of 0→50% ethyl acetate hexanes over 25 minutes to yield the title compound (16.60 g, 111.23 mmol). MS(ESI), m/z 150 (M+1).

Workup

  1. additionOnce the substrate is added
  2. temperaturewarm
  3. customthe reaction to ambient temperature for 3 hours
  4. concentrationConcentrate
  5. customthe reaction
  6. customto remove the ether
  7. temperatureadd anhydrous toluene (200 mL) and heat
  8. temperatureto reflux for 20-21 hours
  9. temperatureCool in an ice bath while slowly and cautiously adding ice
  10. customto quench
  11. customthe reaction
  12. extractionAdd water (200 mL) and then extract the aqueous with ethyl acetate (3×250 mL)
  13. customseparate the layers
  14. filtrationPool, desiccate, filter
  15. concentrationconcentrate the organic extracts to an oil

Sources & evidence

ORD record
ord-aee0fc235aba497a8c64591528b55c77
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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