Propiolic Acid → Cgp-47292

Participants

Reaction Conditions

Reaction Steps

A suspension of 10.25 g (158 mmol) of NaN3, 2.5 g (7.76 mmol) of tetrabutylammonium bromide and 25 g (154 mmol) of 2,6-difluorobenzyl chloride in 50 mL of isopropyl acetate was left stirring at 20-25° C. during 14 h until showing completion by TLC. The resultant mixture was washed with 10% NaCl aqueous solution at 0° C. to remove unreacted NaN3 and the organic phase was stirred with a solution of 17.26 g (246 mmol) of propiolic acid in 50 mL of water at 50° C. during 8 h. After cooling to 20-25° C., the pH was adjusted to 3.2-3.4 by addition of 30% aqueous solution of NaOH and, after one hour at 20-25° C., the suspension was filtered. The solid was further washed with 25 mL of isopropyl acetate precooled at 0-5° C., washed with 40 mL of water dried at 200 mbar and 50° C. to obtain 21.52 g (57.4%) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (purity by UPLC area: 99.94%, 3H-isomer: 0.06%).

Provenance & Evidence