Beta-Alanine → 3-Maleimidopropionic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of maleic anhydride (33.6 g, 377 mmol) and β-alanine (36.96 g, 377 mmol) in 400 mL of acetic acid was added 52 mL toluene, the mixture was an opaque suspension. Heating to 140° C. provided a clear solution, which was refluxed for 5 hours. To the solution was added 50 mL toluene and reflux was continued. In the next 4 hours 31 mL acetic acid/water mixture was separated by distillation using a Dean-Stark apparatus. The reaction mixture was cooled to 90° C. and solvent was removed via distillation with water aspiration. The residue viscous oil was taken up in 200 mL acetone and concentrated. The crude product was purified through a flash chromatography on silica gel with a gradient eluent of 5-12% methanol in dichloromethane to afford 35 g of 1 as white solid. 1H NMR (CDCl3) δ 6.70 (s, 2H), 3.81 (t, 7.2 Hz, 2H), 2.68 (t, 7.2 Hz, 2H), 2.14 (s, 1H).

Provenance & Evidence