Sodium Bicarbonate → 2-Chloro-5-(3,5-dimethylphenyl)nicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a deoxygenated solution of methyl 2-chloro-5-iodonicotinate (1-1, 2.01 g, 6.72 mmol, 1 equiv) and 3,5-dimethylphenylboronic acid (1.01 g, 6.72 mmol. 1.00 equiv) in dioxane (250 mL) was added tetrakis(triphenylphosphine)palladium(0) (155 mg, 0.134 mmol) and 2 N aqueous sodium bicarbonate solution (16.8 mL, 33.6 mmol, 5.00 equiv) and the reaction mixture was heated at 90° C. for 48 hours. The reaction mixture was allowed to cool to 23° C., then partitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL). The aqueous layer was filtered and acidified to pH 2 with concentrated hydrochloric acid. The resulting precipitate was collected by filtration washed with water (2×100 mL) and air dried to afford 2-chloro-5-(3,5-dimethylphenyl)nicotinic acid (1-2) as an off white solid. LRMS m/z (M+H) 262.3 found, 262.1 required.

Provenance & Evidence