Ethyl 2-chloroacetoacetate → 5-Ethyl-2-methyl-nicotinic acid ethyl ester

HRID 3919

Reaction equation

HRID 3919 reaction equation
[CH3:1][CH2:2][C:3]([CH:5]=O)=[CH2:4].C([O-])(=O)C.[NH4+:11].Cl[CH:13]([C:19]([CH3:21])=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15]>C(#N)C>[CH2:2]([C:3]1[CH:5]=[N:11][C:19]([CH3:21])=[C:13]([CH:4]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:1]

Participants

5

Reactant 3

HCID 11858Ethyl 2-chloroacetoacetateHCID 70203EthylacroleinHCID 517165Ammonium Acetate

Product 1

HCID 144366265-Ethyl-2-methyl-nicotinic acid ethyl esterYield 43.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A mixture of ethacrolein (12.8 g 0.152 mole) and ammonium acetate (24.4 g 0.304 mole) in 50 cc acetonitrile is stirred at room temperature and a solution of ethyl 2-chloroacetoacetate (25 g 0.152 mole) in 30 cc acetonitrile is added dropwise over 15 minutes. The reaction mixture is heated at reflux for 16 hours, cooled, and partitioned between water and ethyl acetate. The organic phase is concentrated in vacuo and chromatographed on silica gel using 9:1 hexane-ethylacetate to afford 12.7 g of the title product.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 16 hours
  3. temperaturecooled
  4. custompartitioned between water and ethyl acetate
  5. concentrationThe organic phase is concentrated in vacuo
  6. customchromatographed on silica gel using 9:1 hexane-ethylacetate

Sources & evidence

ORD record
ord-24c7674dbf2448ab81e3a4fd1d43e7e8
Source dataset
uspto-grants-1988_02
Patent number
US04723011

Linked notes

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