Iodine → Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylate

Participants

Reaction Steps

To a slurry of magnesium turnings (0.38 g, 14.4 mmol), a small crystal of iodine and a few drops of dibromoethane in dry tetrahydrofuran (30 mL) under nitrogen was added a solution of 1-bromo-3-chloro-5-fluorobenzene (3 g, 14.4 mmol) in dry tetrahydrofuran (30 mL). The mixture was refluxed for 30 min and then cooled to ambient temperature after which a solution of 1-N-boc-3-pyrrolidone (2.9 g, 15.8 mmol) in a small amount of dry tetrahydrofuran was added. The resulting mixture was stirred at ambient temperature for 2 h after which Aqueous sodium carbonate (10%) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash column chromatography on silica gel (isooctane/ethyl acetate, 1:0 to 1:1) gave the title compound (1.6 g). MS m/z (relative intensity, 70 eV) 315 (M+, 1), 259 (99), 214 (99), 143 (65), 57 (bp).

Provenance & Evidence