Sulfuric Acid → 1-(2-Methylpyridin-4-yl)ethan-1-one

HRID 1617606Notes

Reaction equation

HRID 1617606 reaction equation
C(O[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[CH:6]=1)C.[C:13](OC(C)(C)C)(=O)C.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].S(=O)(=O)(O)O>CCCCCCC.O>[CH3:11][C:7]1[CH:6]=[C:5]([C:4](=[O:12])[CH3:13])[CH:10]=[CH:9][N:8]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 10908tert-Butyl acetateHCID 2733832Lithium HexamethyldisilazideHCID 12243767Ethyl 2-methylisonicotinate

Product 1

HCID 207050141-(2-Methylpyridin-4-yl)ethan-1-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8900HeptaneSolvent

Procedure

To a solution of 2-methyl-isonicotinic acid ethyl ester (3.20 g) and tert-butyl acetate in n-heptane at −5° C. was slowly added lithium hexamethyldisilazide (46.5 mL; 1 M solution in THF). After stirring for 2 h, a solution of sulfuric acid (4.13 mL) in water (20 mL) was added within 20 min keeping the reaction temperature below 10° C. After the addition was completed, the reaction mixture was heated to reflux overnight. Extraction over a sat. solution of NaHCO3 (100 mL) with ethyl acetate (3×50 mL) and drying of the combined organic phases over Na2SO4 provided after evaporation of the organic solvent the title compound as a light brown liquid (2.40 g, 92%), which was used for the consecutive step without any further purification, MS (ESI+): m/z=136.0 [M+H]+.

Workup

  1. customat −5° C.
  2. customthe reaction temperature below 10° C
  3. additionAfter the addition
  4. temperaturethe reaction mixture was heated
  5. temperatureto reflux overnight
  6. extractionExtraction over a sat. solution of NaHCO3 (100 mL) with ethyl acetate (3×50 mL)
  7. dry with materialdrying of the combined organic phases over Na2SO4
  8. customprovided
  9. customafter evaporation of the organic solvent the title compound as a light brown liquid (2.40 g, 92%), which
  10. customwas used for the consecutive step without any further purification, MS (ESI+)

Sources & evidence

ORD record
ord-d073c4604a6a4fa98d968f651ff0d25b
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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