Chloroacetic Acid → (4-Acetylanilino)acetic acid

Participants

Reaction Steps

Chloroacetic acid (40 mmol) was neutralized with aqueous 2N NaOH (50 mmol), then 4-aminoacetophenone was added (25 mmol) was added to the above solution, and the whole reaction mixture was refluxed for 5 hrs. Cooled the reaction mixture, and the solid separated was filtered and washed with water. The solid was recrystallized from aqueous ethanol to get pure 2-((4-acetylphenyl)amino)acetic acid (4.2 g, 90% yield). To a solution of 1-(4-methoxyphenyl)piperazine (0.6 mmol) and 2-((4-acetylphenyl)amino)acetic acid (0.66 mmol) (obtained from the above reaction step) and DMAP (cat) in dichloromethane was added EDCI (0.8 mmol), and the resulting reaction mixture was stirred for 8 h. The reaction mixture was diluted with ethyl acetate and washed with dilute HCl solution, saturated NaHCO3 solution, water and brine solution. Dried the solution with sodium sulfate and concentrated to give crude mass which on silica gel chromatography eluting with 0.6% methanol in dichloromethane provided TG2-150 (70% yield). Similar synthetic procedures were used for making the compounds listed in Table 1 and Table 2.

Provenance & Evidence