2-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester → ethyl 5-amino-1-cyclohexyl-1H-pyrazole-4-carboxylate

HRID 12878

Reaction equation

Cl.[CH:2]1([NH:8][NH2:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(O[CH:13]=[C:14]([C:20]#[N:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16])C.C([O-])(=O)C.[Na+]>C(O)C>[CH2:18]([O:17][C:15]([C:14]1[CH:13]=[N:9][N:8]([CH:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]2)[C:20]=1[NH2:21])=[O:16])[CH3:19]

Participants

Conditions

Temperature: 70 °C

Procedure

Cyclohexylhydrazine hydrochloride (3.057 g, 20.29 mmol, CAS #24214-73-1, purchased from Aldrich) was combined with ethyl (ethoxymethylene)-cyanoacetate (3.390 g, 20.04 mmol) and anhydrous sodium acetate (2.080 g, 25.36 mmol) in 30 mL ethanol. The mixture was heated at 70° C. for 16 hours then cooled to room temperature and concentrated. The residue was partitioned between methylene chloride and water. The separated aqueous phase was extracted with a second portion of methylene chloride. The organic phases were successively washed with water and brine and then combined, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography eluting with a gradient of 25-70% ethyl acetate/hexanes to give 5-amino-1-cyclohexyl-1H-pyrazole-4-carboxylic acid ethyl ester (4.42 g, 92%). Mass spectrum: m/z: 238.1 (M+H).

Workup

temperaturethen cooled to room temperature
concentrationconcentrated
customThe residue was partitioned between methylene chloride and water
extractionThe separated aqueous phase was extracted with a second portion of methylene chloride
washThe organic phases were successively washed with water and brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography
washeluting with a gradient of 25-70% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-5ca9e47eaaeb489c8850e026eadd480c
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728029B2

Linked notes

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