Ethanol → Diethyl 2-(((6-methoxypyridin-3-yl)amino)methylene)malonate

HRID 1422686Notes

Reaction equation

HRID 1422686 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[CH2:10]([O:12][C:13](=[O:24])[C:14](=[CH:20]OCC)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:11].C(O)C>C1(C)C=CC=CC=1>[CH2:10]([O:12][C:13](=[O:24])[C:14](=[CH:20][NH:1][C:2]1[CH:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:11]

Participants

5

Reactant 3

HCID 702EthanolHCID 6871Diethyl (ethoxymethylene)malonateHCID 811216-Methoxy-3-pyridinylamine

Product 1

HCID 619151Diethyl 2-(((6-methoxypyridin-3-yl)amino)methylene)malonateYield 91.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 3-amino-6-methoxy-pyridine (200.0 g, 1611.05 mmol, 1.0 eq) and 2-ethoxymethylene-malonic acid diethyl ester (348.4 g, 1611.05 mmol, 1.0 eq) in toluene (650 mL) is heated to reflux and the ethanol formed is removed by azeotropic distillation. After 2.5 hours at 115° C., the reaction mixture is cooled to room temperature, the solvent is removed and the resulting solid is washed with 500 mL of hexane then dried under vacuum to afford 2-[(6-methoxy-pyridin-3-ylamino)-methylene]malonic acid diethyl ester as a red solid (434.0 g, 90% yield).

Workup

  1. temperatureto reflux
  2. customis removed by azeotropic distillation
  3. customthe solvent is removed
  4. washthe resulting solid is washed with 500 mL of hexane
  5. customthen dried under vacuum

Sources & evidence

ORD record
ord-4e52f22702034b25b21115a0efe35442
Source dataset
uspto-grants-2015_01
Patent number
US08927542B2

Reaction notes

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