Hydrochloric Acid → (2,5-Dichloro-pyridin-3-yl)-acetic Acid Methyl Ester

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of diisopropyl amine (1.21 mL, 9.0 mmol) in tetrahydrofuran (100 mL) was added n-butyl lithium (3.45 mL, 2.5 M in hexanes, 9.0 mmol). The reaction mixture was stirred at −78° C. for 20 minute and 0° C. for 15 minutes, and then cooled to −110° C. To the cooled reaction mixture was added dimethoxymethyl diphenyl phosphine oxide (2.18 g, 8.0 mmol) in tetrahydrofuran (120 mL) and then 2,5-dichloro-pyridine-3-carbaldehyde (1.37 g, 8.0 mmol) in tetrahydrofuran (15 mL) while keeping the reaction temperature less than −100° C. The reaction mixture was stirred at −110° C. for 45 minutes and then quenched with water (50 mL), extracted with diethyl ether and washed with brine. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting residue was azeotroped with toluene and then dissolved in tetrahydrofuran (80 mL) and treated with potassium tert-butoxide (0.97 g, 9.0 mmol) at ambient temperature. After stirring for 2 hours the dark solution was treated with 1N hydrochloric acid and extracted with diethyl ether. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel gave the title compound (0.61 g).

Provenance & Evidence