3-Fluoroacetophenone → 1-(3-Fluorophenyl)-2-(5-trifluoromethyl-2-pyridinyl)ethanone

HRID 354238Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.[CH3:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=1)=[O:14].[H-].[Na+].[NH4+].[Cl-]>COCCOC>[F:21][C:17]1[CH:16]=[C:15]([C:13](=[O:14])[CH2:12][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 42.5 °C

Procedure

A reaction vessel was charged with 2-chloro-5-trifluoromethylpyridine (8 g, 44 mmol), 3-fluoroacetophenone (6.4 g, 46 mmol) and DME (56 ml). Sodium hydride (as a 60% oil dispersion, 5.8 g, 145 mmol) was added in portions to the mixture under nitrogen at room temperature. The mixture was stirred at 40-45° C. overnight. Upon the completion of the reaction, aqueous NH4Cl solution (240 ml) was added to the reaction mixture at room temperature. The mixture was stirred for 0.5 hr and filtered. The cake was washed with water, slurried in hexanes (32 ml) and dried in a vacuum oven to give 10.44 g (84%) of the title compound (a mixture of ketone and enol isomers) as a solid with purity 99% AUC by HPLC (Phenomenex Luna 3μ cyano, 100 mm×4.6 mm. Flow rate: 1 ml/min. UV detection: 220 nm. Eluent: 75% A, 25% B. A: 80/20/0.05 water/acetonitrile/TFA. B: 20/80/0.05 water/acetonitrile/TFA ).

Workup

additionwas added to the reaction mixture at room temperature
stirringThe mixture was stirred for 0.5 hr
filtrationfiltered
washThe cake was washed with water
customdried in a vacuum oven

Sources & evidence

ORD record: ord-52a30f1acfa54175929863fcf3ffd3a6
Source dataset: uspto-grants-2004_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06756498B2

Reaction notes

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