Ethyl Acetoacetate → Ethyl 2-(1-methyl-3-nitro-2-oxo-1,2-dihydropyridin-4-yl)-3-oxobutanoate

HRID 1526969Notes

Reaction equation

HRID 1526969 reaction equation
[O:1]=[C:2]([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].Cl[C:13]1[CH:18]=[CH:17][N:16]([CH3:19])[C:15](=[O:20])[C:14]=1[N+:21]([O-:23])=[O:22]>O1CCCC1>[CH3:19][N:16]1[CH:17]=[CH:18][C:13]([CH:3]([C:2](=[O:1])[CH3:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[C:14]([N+:21]([O-:23])=[O:22])[C:15]1=[O:20]

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 224903014-Chloro-1-methyl-3-nitro-1,2-dihydropyridin-2-one

Product 1

HCID 89739130Ethyl 2-(1-methyl-3-nitro-2-oxo-1,2-dihydropyridin-4-yl)-3-oxobutanoateYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of ethyl 3-oxobutanoate (2.5 g, 19 mmol) in tetrahydrofuran (50 mL) was added sodium hydride (60% w/w, 0.96 g, 23.9 mmol) in batches at 0° C. The mixture was stirred at room temperature for 30 minutes. Then the solution of 4-chloro-1-methyl-3-nitropyridin-2(1H)-one (3.0 g, 16 mmol) in tetrahydrofuran (50 mL) was added in one portion. The resultant solution was stirred and heated to 50° C. for 12 hours. Once the starting material had been consumed, the reaction solution was quenched with water (100 mL) at 0° C., and extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with brine (100 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=10:1) to give ethyl 2-(1-methyl-3-nitro-2-oxo-1,2-dihydropyridin-4-yl)-3-oxobutanoate (2.5 g, 56%) as a yellow solid. LRMS (M+H+) m/z: calcd 282.09. found 282.

Workup

  1. temperatureheated to 50° C. for 12 hours
  2. customOnce the starting material had been consumed
  3. customthe reaction solution was quenched with water (100 mL) at 0° C.
  4. extractionextracted with ethyl acetate (100 mL×3)
  5. washThe combined organic layers were washed with brine (100 mL×2)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue
  10. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=10:1)

Sources & evidence

ORD record
ord-efe4de144190494e92b53b5e90e52991
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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