Acetic Acid → Ethyl 2-(3-Chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate

HRID 1513373Notes

Reaction equation

[O-]CC.[Na+].[Cl:5][C:6]1[C:7]([NH:12][NH2:13])=[N:8][CH:9]=[CH:10][CH:11]=1.[C:14](OCC)(=[O:22])/[CH:15]=[CH:16]\[C:17]([O:19][CH2:20][CH3:21])=[O:18].C(O)(=O)C>O.C(O)C>[Cl:5][C:6]1[C:7]([N:12]2[CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][C:14](=[O:22])[NH:13]2)=[N:8][CH:9]=[CH:10][CH:11]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a 1000 mL flask, anhydrous ethanol (300 mL), sodium ethoxide (16.97 g, 0.249 mol) and 3-chloro-2-hydrazinylpyridine (30.47 g, 98%, 0.21 mol) were added. The reaction mixture was heated to reflux for 5 minutes. Diethyl maleate (36.0 g, 0.31 mol) was added dropwise and heated to reflux for 10 minutes. After being cooled to 65° C., the reaction mixture was neutralized with glacial acetic acid (45.36 g, 0.42 mol) and then diluted with 300 mL water. The reaction mixture was cooled down to room temperature, solid is separated to be filtered, washed with 40% aqueous solution of ethanol (3×50 mL) and dried to give ethyl 1-(3-chloro-2-pyridinyl)-3-oxopyrazolidine-5-carboxylate (31.03 g) as an orange solid in 52% yield. HPLC area normalization method content is 94% (Analytical condition: chromatographic column: ZORBAX Eclipse XDB-C8 4.6×150 mm 5 μm, mobile phase:the ratio of acetonitrile to water is 70:30).

Workup

temperatureThe reaction mixture was heated
temperatureto reflux for 5 minutes
temperatureheated
temperatureto reflux for 10 minutes
temperatureThe reaction mixture was cooled down to room temperature
customsolid is separated
filtrationto be filtered
washwashed with 40% aqueous solution of ethanol (3×50 mL)
customdried

Sources & evidence

ORD record: ord-656005f348b74bda86016816be34f31e
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217179B2

Reaction notes

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