Isobutylene → L-Proline 1,1-dimethylethyl ester

Participants

Reaction Steps

It was found that reaction of proline and excess isobutylene in methylene chloride using anhydrous benzenesulfonic acid in situ to effect phase transfer and N-protection of free proline (solubilization via protonation) afforded an 80% assay yield of proline t-butyl ester. This equilibrium reaction required three days to complete at 0°-5° C. at an optimized charge ratio of proline:benzenesulfonic acid:isobutylene of 1:1.5:12. A strongly basic workup neutralized the benzenesulfonate salts and freed the t-butyl ester for extraction into a neutral organic solvent. The product was typically used as a solution in methylene chloride or alternatively isolated in pure form by concentration and vacuum distillation.

Provenance & Evidence