Water → Dimethyl [2-oxo-2-(pyridin-3-yl)ethyl]phosphonate

HRID 1492556Notes

Reaction equation

HRID 1492556 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([Li])CCC.[C:13](OC)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=1.O>O1CCCC1.CCCCCC>[O:20]=[C:13]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[CH2:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 7151Methyl NicotinateHCID 12958Dimethyl methylphosphonateHCID 178418339Butyllithium

Product 1

HCID 18950746Dimethyl [2-oxo-2-(pyridin-3-yl)ethyl]phosphonateYield 68.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

In argon atmosphere, 15.19 g of dimethyl methylphosphonate was dissolved in 170 ml of dry tetrahydrofuran, followed by dropwise addition of 1.55M n-butyl lithium solution in hexane at -78° C., which was then stirred at the same temperature for 80 minutes. Methyl nicotinate (16.79 g) dissolved in 50 ml of dry tetrahydrofuran was added dropwise and stirred at -78° C. for 20 hours, followed by addition of water. The organic solvent was distilled off under reduced pressure, which was extracted with methylene chloride. Alternatively, 2N hydrogen chloride was added to aqueous phase for neutralization, which was then extracted with ethyl acetate. The organic phase was washed in saturated aqueous sodium chloride, and dried over magnesium sulfate, to distill off the solvent under reduced pressure. The obtained residue was subjected to chromatography on a silica gel column, and from a fraction eluted with methanol-methylene chloride (5:95 v/v), 19.30 g of dimethyl 2-oxo-2-(3-pyridyl)ethylphosphonate was obtained.

Workup

  1. additionwas added dropwise
  2. stirringstirred at -78° C. for 20 hours
  3. distillationThe organic solvent was distilled off under reduced pressure, which
  4. extractionwas extracted with methylene chloride
  5. additionAlternatively, 2N hydrogen chloride was added to aqueous phase for neutralization, which
  6. extractionwas then extracted with ethyl acetate
  7. washThe organic phase was washed in saturated aqueous sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. distillationto distill off the solvent under reduced pressure
  10. washfrom a fraction eluted with methanol-methylene chloride (5:95 v/v)

Sources & evidence

ORD record
ord-94ee9b6f3f254c83b0c9188d4c4d90d9
Source dataset
uspto-grants-1994_12
Patent number
US05374641

Reaction notes

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