Iodine → 1-Benzyl-3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol

Participants

Reaction Steps

To a solution of 1-bromo-3-chloro-5-fluorobenzene (5 g, 23.9 mmol) in dry tetrahydrofuran (50 mL), under nitrogen, was added magnesium turnings (0.58 g, 26.2 mmol) and one crystal of iodine. The mixture was heated until self sustained reflux started. When the reflux ceased a solution of 1-N-benzyl-3-pyrrolidone (4.17 g, 23.9 mmol) in dry tetrahydrofuran (50 mL) was added drop wise. The resulting mixture was stirred at ambient temperature for 15 min after which aqueous saturated ammonium chloride solution (40 mL) was added. The aqueous phase was extracted with tert-butyl methyl ether the combined organic phases were extracted with aqueous HCl (10%, 200 mL), the aqueous phase was basified with aqueous NaOH (5 M) and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was dried (MgSO4), filtered and evaporated. Purification on silica gel (isooctane/ethyl acetate, 1:1 to 0:1) gave the title compound (0.92 g).

Provenance & Evidence