Dimethylacetamide → 1-(5-Fluoropyridin-2-yl)ethan-1-one

HRID 1880610Notes

Reaction equation

HRID 1880610 reaction equation
[Li]C(CC)C.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][N:8]=1.CN(C)[C:16](=[O:18])[CH3:17]>CCOCC>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:16](=[O:18])[CH3:17])=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 31374DimethylacetamideHCID 27831712-Bromo-5-fluoropyridineHCID 178418400CID 53628100

Product 1

HCID 598688311-(5-Fluoropyridin-2-yl)ethan-1-oneYield 53.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

sec-BuLi (1.9 mL, 1.4 M in hexane) was added drop wise to a solution of 2-bromo-5-fluoropyridine (500 mg, 2.8 mmol) in dry Et2O (6 mL) at −78° C. Stirring was continued at this temperature for 10 minutes, after which a solution of N,N-dimethylacetamide (290 μL, 3.1 mmol) in dry Et2O (1 mL) was added drop wise. Stirring was continued at −78° C. for 1 h, where after the reaction mixture was allowed to slowly reach rt. The reaction mixture was again cooled to −78° C. and was quenched by adding 1M HCl aq. solution (6 mL) before it was left to warm to rt over night. The water and organic phases were separated and the water phase extracted with Et2O (2×10 mL). Combined organics were washed with water and brine and dried (MgSO4). After filtration and Careful! evaporation (the title compound is volatile) the red/brown oily crude was dissolved in CH2Cl2 and a small amount of SiO2 was added. The suspension was filtered through a pad of Celite and the solvent was removed by evaporation to give the title compound (203 mg, 1.5 mmol, 52%) as an orange oil. The product was considered to be pure enough to be used directly in the next step without prior purification.

Workup

  1. stirringStirring
  2. waitwas continued at −78° C. for 1 h
  3. customwas allowed to slowly reach rt
  4. customwas quenched
  5. additionby adding 1M HCl aq. solution (6 mL) before it
  6. waitwas left
  7. temperatureto warm to rt over night
  8. customThe water and organic phases were separated
  9. extractionthe water phase extracted with Et2O (2×10 mL)
  10. washCombined organics were washed with water and brine
  11. dry with materialdried (MgSO4)
  12. filtrationAfter filtration and Careful
  13. customevaporation (the title compound
  14. dissolutionwas dissolved in CH2Cl2
  15. additiona small amount of SiO2 was added
  16. filtrationThe suspension was filtered through a pad of Celite
  17. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-5b10e9fc3e9a4eb1b67628bf7592bf69
Source dataset
uspto-grants-2012_11
Patent number
US08318768B2

Reaction notes

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