Sodium Carbonate → 2-(4-Trifluoromethyl-phenyl)-nicotinic acid ethyl ester

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Reaction Steps

Ethyl 2-chloro-nicotinate (1.86 g, 10.0 mmol) was dissolved in 10 ml of dimethoxyethane. Tetrakis(triphenylphosphine)palladium (347 mg, 0.3 mmol) was added and the reaction vessel purged by alternating vacuum and nitrogen gas three times. A solution of 4-trifluoromethylphenylboronic acid (2.09 g, 11.0 mmol) in 20 ml of dimethoxyethane was added to the reaction mixture followed by 10 ml of a 2M sodium carbonate solution. The reaction mixture was heated at 90 C. for 1.5 h before being cooled and extracted with 150 ml of ether. The organic layer was washed with 50 ml of 2N NaOH, 2×50 ml water, and brine before being dried (magnesium sulfate), filtered and concentrated under vacuum to afford 3.24 g of a brown oil. This material was purified by silica gel chromatography eluting with 5 to 10% ethyl acetate in hexanes to afford 2.34 g of the title compound as a pale yellow oil.

Provenance & Evidence