Ammonium Chloride → Tert-butyl 3-(3-chloro-2-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylate

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Reaction Steps

To a solution of 1-bromo-3-chloro-2-fluorobenzene (5.0 g, 23.8 mmol) in dry tetrahydrofuran (50 mL) under nitrogen at −78° C., was added dropwise n-butyllithium (2.5 M in tetrahydrofuran, 9.5 mL, 23.8 mmol). The mixture was stirred for 0.5 h at −78° C. after which a solution of 1-N-boc-3-pyrrolidinone (4.37 g, 23.8 mmol) in dry tetrahydrofuran (20 mL) was added drop wise. The resulting mixture was brought to ambient temperature, aqueous saturated ammonium chloride (50 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic phase was dried (MgSO4), filtered and evaporated. Purification by flash column chromatography on silica gel (ethyl acetate/methanol, 4:1 to 1:1) gave the title compound (4.42 g). MS m/z (rel. intensity, 70 eV) 315 (M+, 1), 259 (16), 214 (31), 157 (17), 57 (bp).

Provenance & Evidence