Bromoacetic Acid → 2-((1-((Tert-butoxy)carbonyl)piperidin-4-yl)oxy)acetic acid

Participants

Reaction Steps

Sodium hydride (596 mg of a 60% dispersion in oil, 14.9 mmol) was added portionwise to a stirred solution of tert-butyl-4-hydroxypiperidine-1-carboxylate (1.0 g, 5 mmol) in anhydrous THF (20 ml) at rt. After 15 min, bromoacetic acid (1.38 g, 9.94 mmol) was introduced and stirring continued for 5 h. Additional bromoacetic acid (5 mmol) and sodium hydride (5 mmol) were added and stirring continued for 24 h. The reaction was quenched with water (2 ml) and diluted with EtOAc (20 ml), which was washed with saturated aqueous NaHCO3 (20 ml). Using dilute HCl, the aqueous phase was acidified to pH 2 and the precipitate extracted into EtOAc (50 ml). The organic phase was dried (MgSO4), evaporated and the residue was purified by flash chromatography (5% AcOH in IH-EtOAc, 7:3 to 1:1) to afford the title acid: RT=2.89 min; m/z (ES+)=260.3 [M+H]+.

Provenance & Evidence