Hydrochloric Acid → 1-(2-Isobutyl-4-pyridyl)-4-methyl-pentanone

HRID 660035Notes

Reaction equation

HRID 660035 reaction equation
[Mg].Br[CH2:3][CH2:4][CH:5]([CH3:7])[CH3:6].[C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH:11]=1)#N.Cl.[OH-:21].[Na+]>BrC=CBr.CCOCC>[CH2:4]([C:3]1[CH:8]=[C:10]([CH2:11][C:12](=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:15]=[CH:14][N:13]=1)[CH:5]([CH3:7])[CH3:6]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 78911-Bromo-3-methylbutaneHCID 14798Sodium HydroxideHCID 5462224MagnesiumHCID 146417864-Cyano-2-isobutylpyridine

Product 1

HCID 689146611-(2-Isobutyl-4-pyridyl)-4-methyl-pentanoneYield 75%

Reagents, catalysts & solvents 2

HCID 108971,2-DibromoetheneCatalystHCID 3283Diethyl EtherSolvent3×

Procedure

Anhydrous Et2O (30 mL) was added to magnesium turnings (1.114 g, 45.8 mmol) in a flame-dried flask. Addition of one drop of dibromoethylene was followed by slow addition of 1-bromo-3-methylbutane (5.895 g, 39.0 mmol) in 20 mL of anhydrous ether at a rate that kept the reaction mixture under reflux. Once the addition was completed the reaction was refluxed for 1 h and cooled to RT. The mixture was then added via cannula to a solution of 4-cyano-2-isobutylpyridine (3.000 g, 18.7 mmol) in 30 mL of anhydrous ether at 0° C. The mixture was stirred at RT for 30 min. and then refluxed for 3 h. The solution was cooled down to RT, poured into 200 mL of 0.5M HCl, and stirred for 30 min. A solution of 1M NaOH was added dropwise until the solution reached pH 9 and the resulting mixture was then extracted with ether (×3), dried with Na2SO4 and concentrated under vacuum. The resulting dark oil was purified by flash chromatography using 1:5 EtOAc/Hexane to give a brown oil (3.296 g, 75%); 1H NMR (400 MHz, CDCl3): δ 0.94-0.98 (m, 12H), 1.61-1.66 (m, 3H), 2.15 (m, 1H), 2.75 (d, J=6.8 Hz, 2H), 2.97 (dd, J=7.2 Hz, J2=7.6 Hz, 2H), 7.54 (m, 2H), 8.71 (d, J=4.8 Hz, 1H); C NMR (100 MHz, CDCl3): δ 22.4, 27.7, 29.3, 32.7, 36.9, 47.6, 118.4, 120.7, 143.2, 150.3, 163.1, 200.3; HRMS-EI (m/z): [M+H+] calcd for [C15H24NO]+, 234.1858. found, 234.1856.

Workup

  1. temperatureunder reflux
  2. additionOnce the addition
  3. temperaturewas refluxed for 1 h
  4. temperaturerefluxed for 3 h
  5. temperatureThe solution was cooled down to RT
  6. stirringstirred for 30 min
  7. extractionthe resulting mixture was then extracted with ether (×3)
  8. dry with materialdried with Na2SO4
  9. concentrationconcentrated under vacuum
  10. customThe resulting dark oil was purified by flash chromatography

Sources & evidence

ORD record
ord-a358e27f22674ccfbe900a70248f52df
Source dataset
uspto-grants-2011_12
Patent number
US08084471B2

Reaction notes

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