Ammonium Chloride → 1-(1-Methyl-1H-pyrazol-5-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-yn-1-one

HRID 238377

Reaction equation

C[Mg]Br.[C:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)#[CH:5].CON(C)[C:19]([C:21]1[N:25]([CH3:26])[N:24]=[CH:23][CH:22]=1)=[O:20].[Cl-].[NH4+]>O1CCCC1>[CH3:26][N:25]1[C:21]([C:19](=[O:20])[C:5]#[C:4][C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:8][CH:7]=2)=[CH:22][CH:23]=[N:24]1

Participants

Conditions

Temperature: -78 °C

Procedure

Methyl magnesium bromide (9.70 mL, 1.0 M tetrahydrofuran solution) was added dropwise to a tetrahydrofuran (4.0 mL) solution of 1-ethynyl-4-(trifluoromethyl)benzene (1.80 mL) under cooling in an ice bath, and the obtained solution was then stirred for 2 hours. Thereafter, the reaction solution was cooled to −78° C., and a tetrahydrofuran (6.2 mL) solution of N-methoxy-N,1-dimethyl-1H-pyrazol-5-carboxamide (867 mg) was then added thereto. The obtained mixture was stirred for 1 hour, and was then stirred for 2.5 hours under cooling in an ice bath. Thereafter, a saturated ammonium chloride aqueous solution was added to the reaction solution, and the obtained mixture was then extracted with ethyl acetate. The organic layer was washed with a saturated saline, and was then dried over anhydrous magnesium sulfate, followed by vacuum concentration. The residue was purified by column chromatography (silica gel cartridge, hexane:ethyl acetate=9:1), so as to obtain the title compound (1.09 g) in the form of a yellow oily substance.

Workup

temperatureunder cooling in an ice bath
stirringThe obtained mixture was stirred for 1 hour
stirringwas then stirred for 2.5 hours
temperatureunder cooling in an ice bath
extractionthe obtained mixture was then extracted with ethyl acetate
washThe organic layer was washed with a saturated saline
dry with materialwas then dried over anhydrous magnesium sulfate
concentrationfollowed by vacuum concentration
customThe residue was purified by column chromatography (silica gel cartridge, hexane:ethyl acetate=9:1)

Sources & evidence

ORD record: ord-1e143a062e8842108de2bd636e760884
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642626B2

Linked notes

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