Water → 1-cyclobutyl-3-(4-isopropoxyphenyl)-1H-pyrazole-4-carbaldehyde

HRID 526776Notes

Reaction equation

Cl.[CH3:2][CH:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:16]([CH:17]=[O:18])=[CH:15][NH:14][N:13]=2)=[CH:8][CH:7]=1)[CH3:4].C([O-])([O-])=O.[K+].[K+].Br[CH:26]1[CH2:29][CH2:28][CH2:27]1.O>C(#N)C.CCOC(C)=O>[CH:26]1([N:14]2[CH:15]=[C:16]([CH:17]=[O:18])[C:12]([C:9]3[CH:10]=[CH:11][C:6]([O:5][CH:3]([CH3:2])[CH3:4])=[CH:7][CH:8]=3)=[N:13]2)[CH2:29][CH2:28][CH2:27]1

Participants

Conditions

Temperature: 2.5 °C

Procedure

A mixture of 3-[4-(propan-2-yloxy)phenyl]-1H-pyrazole-4-carbaldehyde hydrochloride (250 mg, 0.9 mmol) and K2CO3 (626 mg, 4.5 mmol) in acetonitrile (5 ml) was stirred at 0-5° C. for 1 h. Bromocyclobutane (158 mg, 1.16 mmol) was added and the reaction mixture stirred at ambient temperature for 34 h. The reaction was poured into water (200 mL) and extracted with EtOAc (50 mL×3). The combined extracts was washed with brine (100 mL), dried, and concentrated under vacuum. The residue was purified by SGC using Hexane: EtOAc (0%-40%) as eluent to afford 1-cyclobutyl-3-(4-isopropoxyphenyl)-1H-pyrazole-4-carbaldehyde (218 mg, Yield: 71%) as a white solid. LCMS (method C): RT=2.54 min, m/z=285.2 [M+H]+.

Workup

stirringthe reaction mixture stirred at ambient temperature for 34 h
extractionextracted with EtOAc (50 mL×3)
washThe combined extracts was washed with brine (100 mL)
customdried
concentrationconcentrated under vacuum
customThe residue was purified by SGC

Sources & evidence

ORD record: ord-93b92f2fb99f40769b26f14143deacbd
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346761B2

Reaction notes

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