Pyrrolidine → Ethyl 3-chloro-4-(pyrrolidin-1-yl)benzoate

Participants

Reaction Steps

A mixture of ethyl 4-bromo-3-chlorobenzoate (D16) (2.53 g, 9.62 mmol), pyrrolidine (1.03 mL, 12.5 mmol), sodium tert-butoxide (1.29 g, 13.5 mmol), BINAP (196 mg, 0.29 mmol) and tris(dibenzylideneacetone)dipalladium(0) (58 mg, 0.10 mmol) in toluene (120 mL) was heated to reflux under argon for 3 h. The reaction was allowed to cool and was filtered. The solid was washed with toluene and then the filtrate was concentrated. The residue was partitioned between ethyl acetate (150 mL) and water (100 mL) with aqueous sodium bicarbonate (50 mL) added. The organic phase was dried (phase separator) and concentrated to give an orange oil. The oil was purified by reverse phase chromatography, eluting 5-100% acetonitrile in water to give the title compound as an orange oil (600 mg). This contained some impurities. MS (ES): C13H1635ClNO2 requires 253; found 254 (MH+).

Provenance & Evidence