Sodium ethoxide → Ethyl 5-oxo-2-(pyridin-3-yl)pyrazolidine-3-carboxylate

HRID 512738Notes

Reaction equation

HRID 512738 reaction equation
[O-]CC.[Na+].Cl.Cl.[NH:7]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)[NH2:8].[C:15](OCC)(=[O:23])/[CH:16]=[CH:17]\[C:18]([O:20][CH2:21][CH3:22])=[O:19]>>[O:23]=[C:15]1[NH:8][N:7]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:16]1

Participants

4

Reactant 3

HCID 2723922Sodium ethoxideHCID 5271566Diethyl MaleateHCID 171324893-Hydrazinylpyridine dihydrochloride

Product 1

HCID 118023220Ethyl 5-oxo-2-(pyridin-3-yl)pyrazolidine-3-carboxylate

Conditions

Temperature
20 °C

Procedure

A 4-neck round bottomed flask (250 mL) was charged with sodium ethoxide (21 wt % in ethanol, 56 mL, 192 mmol). 3-Hydrazinopyridine.dihydrochloride (10.0 g, 55.0 mmol) was added, causing an exotherm from 20° C. to 32° C. The reaction was allowed to cool to 20° C. and diethyl maleate (13.4 mL, 82.0 mmol) was added, and the reaction was heated at 60° C. for 3 hours. The reaction was cooled to 20° C. and quenched with acetic acid. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organics were concentrated to dryness and the residue was purified by flash column chromatography using ethyl acetate as eluent to the title compound as a blue oil (6.60 g, 51%): 1H NMR (400 MHz, DMSO-d6) δ 10.40 (s, 1H), 8.40-8.26 (m, 1H), 8.19 (dd, J=4.4, 1.6 Hz, 1H), 7.47-7.21 (m, 2H), 4.77 (dd, J=9.8, 2.1 Hz, 1H), 4.22 (qd, J=7.1, 1.7 Hz, 2H), 3.05 (dd, J=17.0, 9.8 Hz, 1H), 1.99 (s, 1H), 1.25 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 170.37, 146.60, 142.60, 137.28, 123.54, 121.94, 65.49, 61.32, 32.15, 20.72, 13.94; ESIMS m/z 236 ([M+H]+).

Workup

  1. customfrom 20° C. to 32° C
  2. temperaturethe reaction was heated at 60° C. for 3 hours
  3. temperatureThe reaction was cooled to 20° C.
  4. customquenched with acetic acid
  5. additionThe reaction mixture was diluted with water (100 mL)
  6. extractionextracted with ethyl acetate (3×100 mL)
  7. concentrationThe combined organics were concentrated to dryness
  8. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-53441e8cbe3f4f73aa8ae33b3be57fd4
Source dataset
uspto-grants-2015_08
Patent number
US09102654B2

Reaction notes

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