Sodium Hydroxide → 2-Acetamido-3-(pyridin-2-yl)propanoic acid

HRID 567688Notes

Reaction equation

HRID 567688 reaction equation
C[O-].[Na+].C([CH:6](CC)[C:7]([NH:9][CH:10]([C:14]([O-])=O)[C:11]([O-:13])=[O:12])=[O:8])C.Cl.ClC[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.[OH-].[Na+]>CO.O>[C:7]([NH:9][CH:10]([C:11]([OH:13])=[O:12])[CH2:14][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)(=[O:8])[CH3:6]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 23392Picolyl chloride hydrochlorideHCID 10942334Sodium MethoxideHCID 21751412Diethylacetamidomalonate

Product 1

HCID 212623132-Acetamido-3-(pyridin-2-yl)propanoic acidYield 66%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
45 °C

Procedure

A solution of sodium methoxide (65.8 g, 1.22 mol) in methanol (300 ml) was treated portionwise with diethylacetamidomalonate (132.3 g, 0.61 mol) maintaining a temperature of ca. 45° C. The mixture was then heated under reflux for 15 min. The mixture was cooled to 50° C. then treated slowly with a suspension of 2-chloromethylpyridine hydrochloride (100 g, 0.61 mol), the pink suspension was then heated under reflux for a further 6 h. Water (500 ml) was added followed by 10M sodium hydroxide (122 ml, 1.22 mol) and the pH was maintained at ca. 11 while heating the mixture at 70° C. overnight. The mixture was cooled to RT and the methanol removed in vacuo. The aqueous residue was washed with ethyl acetate (2×500 ml), then acidified to pH 5 and further washed with ethyl acetate (2×500 ml), before evaporating in vacuo to provide a semi-solid. The residue was triturated with hot ethanol (500 ml) and the sodium chloride removed by filtration. The filtrate was then evaporated in vacuo and the residue crystallised from methanol-ethyl acetate to provide the title compound (70 g, 66%) as a yellow solid.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureunder reflux for 15 min
  3. temperatureThe mixture was cooled to 50° C.
  4. temperaturethe pink suspension was then heated
  5. temperatureunder reflux for a further 6 h
  6. temperaturethe pH was maintained at ca. 11
  7. temperaturewhile heating the mixture at 70° C. overnight
  8. temperatureThe mixture was cooled to RT
  9. customthe methanol removed in vacuo
  10. washThe aqueous residue was washed with ethyl acetate (2×500 ml)
  11. washfurther washed with ethyl acetate (2×500 ml)
  12. custombefore evaporating in vacuo
  13. customto provide a semi-solid
  14. customThe residue was triturated with hot ethanol (500 ml)
  15. customthe sodium chloride removed by filtration
  16. customThe filtrate was then evaporated in vacuo
  17. customthe residue crystallised from methanol-ethyl acetate

Sources & evidence

ORD record
ord-4c1471b3971c4fd4acb9f48dbc791f3c
Source dataset
uspto-grants-2001_01
Patent number
US06180611B2

Reaction notes

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