Toluene → Tirbanibulin

Participants

Reaction Conditions

Reaction Steps

The procedure for the amide formation described for the medium scale reaction worked well on large scale. Methyl ester 7 and benzylamine (3 equiv.) were dissolved in anisole and heated at 150° C. for almost 2 days. However, the isolation of the product using the medium-scale procedure can result in a solid mass of product. To avoid this issue, the reaction mixture was not cooled to room temperature, but cooled to 45-50° C. before adding the anti-solvent. Toluene and heptane were used as anti-solvent in the original procedure. Using n-heptane alone provided adequate purity and increased yields from 81 to 90%. Further, the use of a single isomer of heptane was essential to adequately quantitate the residual solvent.

Provenance & Evidence