Diethyl Oxalate → Ethyl 3-(pyridin-3-yl)-1H-pyrazole-5-carboxylate

HRID 872760Notes

Reaction equation

HRID 872760 reaction equation
[Na].[C:2]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)(=O)[CH3:3].[C:11](OCC)(=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13].Cl.[NH2:22][NH2:23].[OH-].[Na+]>C(O)C.O>[N:7]1[CH:8]=[CH:9][CH:10]=[C:5]([C:2]2[CH:3]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:23][N:22]=2)[CH:6]=1

Participants

8

Reactant 5

HCID 7268Diethyl OxalateHCID 95893-AcetylpyridineHCID 14798Sodium HydroxideHCID 115031Hydrazinium chlorideHCID 5360545Sodium

Product 1

HCID 575603Ethyl 3-(pyridin-3-yl)-1H-pyrazole-5-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

Sodium (0.2 g, 13.69 mmol) was dissolved completely in 12 mL of ethanol under nitrogen atmosphere. To this solution was added 3-acetylpyridine (1.499 ml, 13.69 mmol) followed by diethyl oxalate (1.859 ml, 13.69 mmol) at RT with constant stirring. The mixture was then warmed to 75° C. for 3 h. The mixture was then cooled to RT and a solution of hydrazine hydrochloride (0.938 g, 13.69 mmol) in water (2 ml) was added. Further again the solution was warmed to 75° C. for 3 h. After the completion of the reaction as evidenced from the LC-MS, the reaction mixture was cooled and neutralized by 2 M NaOH solution. The crude product was then extracted with ethyl acetate, washed with water and brine. The organic solvent was evaporated and the residue was purified by CombiFlash (eluent: DCM: 10% MeOH/DCM). Yield 1.577 g. 1H NMR (400 MHz; MeOD): δ 1.40 (t, 3H), 4.39 (q, 2H), 7.29 (s, 1H), 7.51 (m, 1H), 8.24 (m, 1H), 8.51 (dd, 1H), 8.99 (d, 1H).

Workup

  1. temperatureThe mixture was then cooled to RT
  2. temperatureFurther again the solution was warmed to 75° C. for 3 h
  3. customAfter the completion of the reaction
  4. temperaturethe reaction mixture was cooled
  5. extractionThe crude product was then extracted with ethyl acetate
  6. washwashed with water and brine
  7. customThe organic solvent was evaporated
  8. customthe residue was purified by CombiFlash (eluent: DCM: 10% MeOH/DCM)

Sources & evidence

ORD record
ord-7f49bf8596034beab5790e8b17f66338
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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