Ethyl 2-formyl-3-oxopropanoate → Ethyl 1-[3-(difluoromethoxy)phenyl]-1H-pyrazole-4-carboxylate

HRID 571842Notes

Reaction equation

Cl.[F:2][CH:3]([F:13])[O:4][C:5]1[CH:6]=[C:7]([NH:11][NH2:12])[CH:8]=[CH:9][CH:10]=1.[CH:14]([CH:16]([CH:22]=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=O>C(O)C.CCCCC>[F:2][CH:3]([F:13])[O:4][C:5]1[CH:6]=[C:7]([N:11]2[CH:22]=[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:14]=[N:12]2)[CH:8]=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(3-(Difluoromethoxy)phenyl)hydrazine hydrochloride (4.2 g, 19.9 mmol; CAS 479581-64-1) was suspended in ethanol (80 ml) and cooled to 0° C. A solution of ethyl 2-formyl-3-oxopropanoate (2.87 g, 19.9 mmol; CAS 80370-42-9) in ethanol (40 ml) was added, and the reaction was stirred overnight. The solvent was removed under reduced pressure and the residue partitioned between sodium bicarbonate solution and ethyl acetate. The organic layers were combined, dried (MgSO4) and evaporated to yield an orange solid. The solid was suspended in pentane (50 ml) and stirred at 35° C. for 90 min. The suspension was cooled in an ice bath for one hour and the solid was filtered and washed with pentane. After drying 5.12 g (91%) of a yellow solid was obtained MS (ISP): 283.1 ([M+H]+).

Workup

customThe solvent was removed under reduced pressure
customthe residue partitioned between sodium bicarbonate solution and ethyl acetate
dry with materialdried (MgSO4)
customevaporated
customto yield an orange solid
stirringstirred at 35° C. for 90 min
temperatureThe suspension was cooled in an ice bath for one hour
filtrationthe solid was filtered
washwashed with pentane
dry with materialAfter drying 5.12 g (91%) of a yellow solid
customwas obtained MS (ISP)

Sources & evidence

ORD record: ord-f786fb10387a41959f629aeb99abb199
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029370B2

Reaction notes

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