Toluene → HCID 17747836, compound

HRID 555955Notes

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]([C:13]1[C:14]([CH3:20])=[N:15][N:16]([CH3:19])[C:17]=1[F:18])=[O:12])(=[O:3])[CH3:2].[CH2:21]([Mg]Cl)[CH:22](C)[CH3:23].[C:27]1(C)C=CC=CC=1.[Cl-].[NH4+]>C1COCC1>[F:18][C:17]1[N:16]([CH3:19])[N:15]=[C:14]([CH3:20])[C:13]=1[C:11]([NH:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C:1]([OH:3])([CH3:27])[CH2:2][CH:22]([CH3:23])[CH3:21])=[O:12]

Participants

Conditions

Temperature: -10 °C

Procedure

Under argon and with stirring at −10° C., N-(2-acetylphenyl)-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (as a solid, 10 g, 36.3 mmol) and isobutylmagnesium chloride (as a 2 M solution in THF, 41.7 ml; 83.55 mmol) are added simultaneously and continuously to 400 ml of toluene over a period of 150 minutes. The mixture is allowed to warm to room temperature, 200 ml of ammonium chloride solution are added, the mixture is extracted three times with in each case 100 ml of ethyl acetate and the organic phases are dried using sodium sulphate and concentrated under reduced pressure. This gives 5-fluoro-N-[2-(1-hydroxy-1,3-dimethylbutyl)phenyl]-1,3-dimethyl-1H-pyrazole-4-carboxamide (14.2 g, purity (GC/MS) 72.8%; 85% of theory) which still contains 14% of starting material.

Workup

temperatureto warm to room temperature
extractionthe mixture is extracted three times with in each case 100 ml of ethyl acetate
customthe organic phases are dried
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-897fadea5e0d4a708ea81576f4d35820
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08053572B2

Reaction notes

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