An optimized protocol for the multigram synthesis of 3-(trifluoromethyl)bicyclo[1.1.1]pent-1-ylglycine (CF3-Bpg)

An optimized procedure for the multigram synthesis of 3-(trifluoromethyl)bicyclo[1.1.1]pent-1-ylglycine (CF₃-Bpg) has been developed. The overall yield of the synthesis for the optimized up-scaling was increased from 35% to 53%. Moreover, conditions for separating the key isomeric aminonitriles 7 and 8 by crystallization were found, which greatly facilitated the isolation of 8 on a multigram scale. Following this optimized protocol, 100 g of optically pure CF₃-Bpg have been synthesized.

Mykhailiuk P. K.; Voievoda N. M.; Afonin S.; Ulrich A. S.; Komarov I. V.
J. Fluorine Chem. 2010, 131 (2), 217-220
DOI: 10.1016/j.jfluchem.2009.10.004