Diethyl Malonate → HCID 67107302, compound

HRID 1910829Notes

Reaction equation

HRID 1910829 reaction equation
[CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[H-].[Na+].ClC(OCC)=O.[C:19]([O:27][CH2:28][CH3:29])(=[O:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22]>C1COCC1.C(O)(=O)C>[CH2:24]([O:23][C:21](=[O:22])[CH:20]([C:4]([C:3]1[C:2]([CH3:1])=[N:10][CH:9]=[CH:8][CH:7]=1)=[O:6])[C:19]([O:27][CH2:28][CH3:29])=[O:26])[CH3:25]

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 10928Ethyl chloroformateHCID 24758Sodium hydride2×HCID 6433732-Methylnicotinic acid

Product 1

HCID 67107302HCID 67107302, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of 2-methyl-nicotinic acid (10.2 g, 74.45 mmol) in THF (30 mL) chilled to −10° C. was added sodium hydride (60% in mineral oil; 3.89 g, 89.3 mmol) portionwise and the reaction mixture stirred till no further gas evolution was noticed. Ethyl chloroformate (6.0 mL, 74.45 mmol) was added slowly at the same temperature and stirring continued for another 1 h, whereby a thick white slurry developed. Simultaneously, in a separate vessel, diethyl malonate (11.9 mL, 74.45 mmol) was added dropwise to a slurry of sodium hydride (60% in mineral oil; 3.24 g, 74.45 mmol)) in THF (20 mL) at −10° C., stirred for 30 min and slowly added to the slurry of the mixed anhydride. The reaction mixture was allowed to warm to r.t. and stirred overnight. The pH was adjusted to ˜pH 6 with acetic acid and evaporated to dryness. The residue was partitioned between water and ethyl acetate, the organics separated, then washed with water, brine, dried over sodium sulfate, filtered and concentrated to yield 2-(2-methyl-pyridine-3-carbonyl)-malonic acid diethyl ester (18.16 g, 87%) as an oil.

Workup

  1. stirringstirring
  2. stirringstirred for 30 min
  3. stirringstirred overnight
  4. customevaporated to dryness
  5. customThe residue was partitioned between water and ethyl acetate
  6. washthe organics separated, then washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-8eeca155ee35489793784377c4ce1ca1
Source dataset
uspto-grants-2013_12
Patent number
US08604029B2

Reaction notes

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