Ethyl 2-(ethoxymethylene)-4,4,4-trifluoroacetoacetate → ethyl 1-(4-cyanophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1799438Notes

Reaction equation

C(O/[CH:4]=[C:5](/[C:11](=O)[C:12]([F:15])([F:14])[F:13])\[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.Cl.[NH:18]([C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1)[NH2:19]>C(O)C>[C:24]([C:23]1[CH:26]=[CH:27][C:20]([N:18]2[C:11]([C:12]([F:13])([F:14])[F:15])=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:4]=[N:19]2)=[CH:21][CH:22]=1)#[N:25]

Participants

Conditions

Temperature: -10 °C

Procedure

A solution of (Z)-ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate (2.41 g, 10.03 mmol) in ethanol (10 mL) was added dropwise to a stirred solution of 4-hydrazinylbenzonitrile hydrochloride (1.702 g, 10.03 mmol), in ethanol (50 mL) cooled to −10° C. The resulting solution was allowed to stir at room temperature for 16 hours. The reaction mixture was evaporated to dryness and the residue redissolved in EtOAc (100 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica (120 g) chromatography, elution gradient 10 to 60% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 1-(4-cyanophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.400 g, 77%) as a white solid.

Workup

customThe reaction mixture was evaporated to dryness
dissolutionthe residue redissolved in EtOAc (100 mL)
washwashed sequentially with water (50 mL) and saturated brine (50 mL)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
customevaporated
customto afford crude product
customThe crude product was purified by flash silica (120 g) chromatography, elution gradient 10 to 60% EtOAc in isohexane
customPure fractions were evaporated to dryness

Sources & evidence

ORD record: ord-f119780c47f848afaa6168558d712634
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344016B2

Reaction notes

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