Methanol → N-(6-phenyl-pyridin-3-yl)-malonamic acid

HRID 1093689Notes

Reaction equation

HRID 1093689 reaction equation
C([O:3][C:4](=[O:21])[CH2:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)=[O:7])C.CO.C1COCC1.O[Li].O>O>[C:15]1([C:12]2[N:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[CH2:5][C:4]([OH:21])=[O:3])=[CH:14][CH:13]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 57875819N-(6-phenyl-pyridin-3-yl)-malonamic acid ethyl ester

Product 1

HCID 57874490N-(6-phenyl-pyridin-3-yl)-malonamic acidYield 82.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of 5-amino-2-phenyl-pyridine (4.0 g, 0.0235 mol) in dichloromethane (40 mL) was added ethyl malonyl chloride (5.307 g, 0.035 mol) dropwise. The resulting mixture was stirred for 1 hour. The mixture was diluted with water and the product was extracted with dichloromethane. The organic layer was washed with saturated sodium bicarbonate solution, brine, dried over Na2SO4 and evaporated to afford 5.46 g (80%) of N-(6-phenyl-pyridin-3-yl)-malonamic acid ethyl ester. To a solution of N-(6-phenyl-pyridin-3-yl)-malonamic acid ethyl ester (5.46 g, 0.019 mol) in the mixture of methanol (27.5 mL), THF (55 mL) and H2O (16.5 mL) was added LiOH.H2O (1.212 g, 0.0288 mol). The resulting reaction mixture was stirred for 1 hour at ambient temperature then concentrated. The resulting residue was diluted with water, acidified with concentrated HCl and the product was extracted with ethyl acetate. The ethyl acetate was washed with brine, dried over Na2SO4 and evaporated under reduced pressure to afford 4.0 g (82%) of N-(6-phenyl-pyridin-3-yl)-malonamic acid.

Workup

  1. customThe resulting reaction mixture
  2. concentrationthen concentrated
  3. additionThe resulting residue was diluted with water
  4. extractionthe product was extracted with ethyl acetate
  5. washThe ethyl acetate was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-20e89214a0a748f983b226736b946b06
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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