Pyrrolidine → 1-(3-Bromo-5-methoxymethoxy-phenyl)-pyrrolidine

Participants

Reaction Conditions

Reaction Steps

A solution of pyrrolidine (1.66 g, 23.27 mmol), in dry tetrahydrofuran (20 ml) was cooled to −78° C. under argon atmosphere. A solution of n-BuLi (15.5 ml, 1.5 M in hexanes) was added via slow drop-wise addition over 5 minutes. After complete addition the cooling bath was removed and the mixture allowed to warm to ice bath temperature over 30 minutes. A second oven dried flask was charged with 1,3-dibromo-5-methoxymethoxy-benzene (5.74 g, 19.4 mmol) and lithium bromide (1.68 g, 19.4 mmol) and taken up in dry tetrahydrofuran (10 ml). This flask was then cooled to 78° C. under argon. The contents of the first flask (slurry containing the lithio salt of pyrrolidine) was taken up in a syringe with wide bore needle and added via drop-wise addition to the second flask (over 10 minutes). The mixture was allowed to slowly warm to ambient temperature over night. The mixture was quenched via the addition of 1 N HCl (23 ml), saturated aqueous NH4Cl (34 ml) and water (40 ml). Ethyl acetate (80 ml) was added and the material shaken in a separtatory funnel. The ethyl acetate phase was collected and washed with an equal volume of 50% diluted brine solution. The aqueous phases were back extracted with ethyl acetate (2×50 ml), the organics combined, dried (MgSO4), filtered and stripped to provide a yellow remainder. The oil was purified by silica gel chromatography using 4%-8% EtOAc in hexanes as eluant to provide 930 mg of 1-(3-Bromo-5-methoxymethoxy-phenyl)-pyrrolidine as a light yellow mobile oil.

Provenance & Evidence