Sodium hydride → (RS)-ethoxy-(3-nitro-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester

HRID 1828093Notes

Reaction equation

HRID 1828093 reaction equation
[H-].[Na+].[OH:3][C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[CH:6][N:5]=1.[CH2:13]([O:15][C:16](=[O:22])[CH:17](Cl)[O:18][CH2:19][CH3:20])[CH3:14]>CN(C=O)C.CCOC(C)=O>[CH2:13]([O:15][C:16](=[O:22])[CH:17]([O:18][CH2:19][CH3:20])[N:5]1[CH:6]=[CH:7][CH:8]=[C:9]([N+:10]([O-:12])=[O:11])[C:4]1=[O:3])[CH3:14]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2724873Ethyl 2-chloro-2-ethoxyacetateHCID 178526677HCID 178526677, compound

Product 1

HCID 86598841(RS)-ethoxy-(3-nitro-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl esterYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 1.228 g=0.74 g NaH) was suspended in DMF (45 ml) under an argon atmosphere. The stirred suspension was cooled to 0° C. and 2-hydroxy-3-nitropyridine (4 g) was added portion wise over a period of 45 min. The mixture containing a compact yellow precipitate was then stirred at r.t. for 30 min and was cooled again to 0C. A solution of 2-chloro-2-ethoxyacetic acid ethyl ester (4.99 g) in DMF (5 ml) was then added and stirring at r.t. was continued for 2 h 30. The mixture was diluted with EtOAc and washed with water. The aqueous phase was extracted with EtOAc. The combined organics were washed with water and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by chromatography (silica gel, gradient cyclohexane=>cyclohexane/EtOAc 3:2) to give (RS)-ethoxy-(3-nitro-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester (4.32 g) as yellow solid. MS 270.1 ([M]+)

Workup

  1. additionThe mixture containing a compact yellow precipitate
  2. stirringstirring at r.t.
  3. waitwas continued for 2 h
  4. washwashed with water
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washThe combined organics were washed with water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography (silica gel, gradient cyclohexane=>cyclohexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-d4b82a2ecf5e48d1b268bfad79a92ea6
Source dataset
uspto-grants-2006_06
Patent number
US07056932B2

Reaction notes

Loading…