Dimethyl Sulfide → 3-Bromo-4-cyclopropyl-5-fluoro-4H-pyridine-1-carboxylic acid phenyl ester

Participants

Reaction Steps

Phenyl chloroformate (0.764 mL, 0.0060 mol) was added to a mixture of copper iodide (1.082 g, 0.0056 mol), dimethylsulphide (2.78 mL, 0.0380 mol) and 3-bromo-5-fluoropyridine (1.0 g, 0.0056 mol) in anhydrous tetrahydofuran (25 mL) at room temperature and the mixture was stirred for 40-50 min. To this suspension cyclopropyl magnesium bromide (12.13 mL, 0.0060 mol, 0.5M solution in tetrahydofuran) was added at −25 to −20° C. over 30-40 min. The mixture was stirred at this temperature for 30 min, and then warmed slowly to room temperature over 1.0-1.5 h. The reaction mixture was quenched with 20% ammonium chloride (25 mL), followed by extraction of the aqueous layer with ethyl acetate (50 mL). The organic layer was washed with 20% ammonium chloride (25 mL), then saturated sodium chloride (25 mL), and dried over anhydrous sodium sulphate. Silica gel chromatography using 0-5% ethyl acetate-hexane gradient yielded crude phenyl 3-bromo-4-cyclopropyl-5-fluoropyridine-1 (4H)-carboxylate MS (M+1): 339.7.

Provenance & Evidence