Diethyl Oxalate → Ethyl 1H,4H,5H,6H-cyclopenta[c]pyrazole-3-carboxylate

HRID 475502Notes

Reaction equation

HRID 475502 reaction equation
[C:1]1(=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:7](OCC)(=O)[C:8]([O:10][CH2:11][CH3:12])=[O:9].CC([O-])(C)C.[K+].Cl.[NH2:24][NH2:25]>CCO.C1COCC1.O>[CH2:11]([O:10][C:8]([C:7]1[C:2]2[CH2:3][CH2:4][CH2:5][C:1]=2[NH:25][N:24]=1)=[O:9])[CH3:12]

Participants

8

Reactant 4

HCID 7268Diethyl OxalateHCID 8452CyclopentanoneHCID 115031Hydrazinium chlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 23005643Ethyl 1H,4H,5H,6H-cyclopenta[c]pyrazole-3-carboxylateYield 71%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of cyclopentanone (42.0 g, 0.50 mol) and diethyl oxalate (73.1 g, 0.50 mol) in EtOH (2.5 L) at rt under N2 was added a solution of KOt-Bu in THF (500 mL of a 1M solution, 0.50 mol) over 0.5 h via an addition funnel. The reaction was stirred for 3.5 h at which time the flask was cooled to 0° C. Hydrazine hydrochloride (37.6 g, 0.55 mol) in H2O (250 mL) was added via addition funnel over 0.5 h. The reaction was warmed to rt and stirred for 16 h. The volatiles were removed in vacuo and the resulting solid was washed with NaHCO3 (sat. aq., 500 mL) and H2O (500 mL). Further concentration in vacuo gave pure 1,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid ethyl ester (63.6 g, 0.35 mol, 71% yield) as a yellow solid.

Workup

  1. temperatureThe reaction was warmed to rt
  2. stirringstirred for 16 h
  3. customThe volatiles were removed in vacuo
  4. washthe resulting solid was washed with NaHCO3 (sat. aq., 500 mL) and H2O (500 mL)
  5. concentrationFurther concentration in vacuo

Sources & evidence

ORD record
ord-5e1cd96642404fb898062fb138e8152f
Source dataset
uspto-grants-2014_01
Patent number
US08637555B2

Reaction notes

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