Acetic Acid → Ethyl 3-(2-chloro-5-nitropyridin-4-yl)-2-oxopropanoate

HRID 1693355Notes

Reaction equation

HRID 1693355 reaction equation
[O-]CC.[K+].[C:5]([O:12][CH2:13][CH3:14])(=[O:11])[C:6]([O:8]CC)=O.[Cl:15][C:16]1[CH:21]=[C:20]([CH3:22])[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=1.C(O)(=O)C>C(OCC)C.C(O)C.O>[CH2:13]([O:12][C:5](=[O:11])[C:6](=[O:8])[CH2:22][C:20]1[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=[C:16]([Cl:15])[CH:21]=1)[CH3:14]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 7268Diethyl OxalateHCID 3453642-Chloro-4-methyl-5-nitropyridineHCID 23670592Potassium ethoxide

Product 1

HCID 53472030Ethyl 3-(2-chloro-5-nitropyridin-4-yl)-2-oxopropanoate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

Route A: To a solution of potassium ethoxide (1.46 g, 17.4 mmol) in diethyl ether (80 mL) and ethanol (10 mL) under an argon atmosphere was added diethyl oxalate (2.4 mL, 17.4 mmol) and the mixture stirred at rt for 0.5 h. A solution of 2-chloro-4-methyl-5-nitropyridine (3.0 g, 17.4 mmol) in diethyl ether (20 mL) was added resulting in the formation of a dark green precipitate. The reaction was stirred at rt for 15 h, cooled to 0° C., filtered and washed with cold diethyl ether to give a dark green solid. The solid was dissolved in water (200 mL) and acidified to pH 4 with acetic acid to give an orange precipitate. The solid was collected by filtration and dried to give the title compound. m/z (ES+)=273 [M+H]+. Route B: To a solution of 2-chloro-4-methyl-5-nitropyridine (1.0 g, 5.8 mmol) in diethyl oxalate (4.23 g, 29 mmol) under an argon atmosphere was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.95 mL, 6.4 mol). The mixture was stirred at rt for 1.5 h then diluted with t-butyl methyl ether (40 mL), water (30 mL) and acetic acid (1 ml). The organic layer was separated, washed with water, dried (MgSO4) and evaporated to dryness. The resultant damp red solid residue was finally dried under high vacuum at 40-50° C. to give the title compound.

Workup

  1. customresulting in the formation of a dark green precipitate
  2. stirringThe reaction was stirred at rt for 15 h
  3. temperaturecooled to 0° C.
  4. filtrationfiltered
  5. washwashed with cold diethyl ether
  6. customto give a dark green solid
  7. customto give an orange precipitate
  8. filtrationThe solid was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-73c6dee1a5db4b12b1c214a3e53c832d
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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