1,4-Dioxane → 1-(5-Ethylpyridin-2-yl)ethanone

HRID 341130Notes

Reaction equation

HRID 341130 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=1.O1CCO[CH2:13][CH2:12]1>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]>[CH2:12]([C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=1)[CH3:13]

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 231453451-(5-Bromopyridin-2-yl)ethan-1-one

Product 1

HCID 231434261-(5-Ethylpyridin-2-yl)ethanone

Reagents, catalysts & solvents 1

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

Conditions

Temperature
50 °C

Procedure

A mixture of 1-(5-bromopyridin-2-yl)ethanone (6.30 g, 31.5 mmol; Supplier=Kalexsyn; Lot=90) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (560 mg, 0.76 mmol) in dioxane (120 ml) was degassed by sparging with N2 for 10 minutes. Added a solution (15% w/w) of diethyl zinc in hexane (50 ml) slowly, dropwise and heated to 50° C. The orange mixture turned dark, ultimately generating a dark orange with yellow solids as it stirred at 50° C. for 30 minutes. Allowed to cool to room temperature. The reaction mixture was partitioned between EtOAc (200 ml) and water (200 ml), and the aqueous phase was extracted 2× with EtOAc. The combined organic phases were washed with brine (500 ml), dried (Na2SO4), filtered and evaporated in vacuo to give 4.14 g brown oil. Distilled under high vac using short-path distillation apparatus. BP=55° C. @ 0.32 torr to give 2.249 g of slightly tinted oil. 1H-NMR (CDCl3): δ 8.50 (d, J=1.9 Hz, 1H), 7.96 (d, J=7.9 Hz, 1H), 7.63 (dd, J=8.0, 2.2 Hz, 1H), 2.71 (m, 2H), 2.69 (s, 3H), 1.27 (t, J=7.6 Hz, 3H). HPLC: 2.011 min., 57 area % @ 210 nm; 2.012 min., 75 area % @ 254 nm. LCMS: MS (ESI—) for C10H12O m/z 150.1 (M+H)+.

Workup

  1. customwas degassed
  2. customby sparging with N2 for 10 minutes
  3. additionAdded a solution (15% w/w) of diethyl zinc in hexane (50 ml) slowly
  4. temperatureAllowed to cool to room temperature
  5. customThe reaction mixture was partitioned between EtOAc (200 ml) and water (200 ml)
  6. extractionthe aqueous phase was extracted 2× with EtOAc
  7. washThe combined organic phases were washed with brine (500 ml)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-5337d2bcc96246dda5b7cb9b2c84f158
Source dataset
uspto-grants-2014_11
Patent number
US08895748B2

Reaction notes

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