Chloroacetic Acid → 2-(4-acetylanilino)acetic acid

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.

1. additionwas added to the above solution
2. customthe whole reaction mixture
3. temperaturewas refluxed for 5 hrs
4. temperatureCooled the reaction mixture
5. customthe solid separated
6. filtrationwas filtered
7. washwashed with water
8. customThe solid was recrystallized from aqueous ethanol

ORD record

ord-76f188d55cc64202866f1715cd8c0858

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428478B2