Chemistry of 4-fluoroglutamic acid. Part 2. Separation of the diastereomers on a large scale. Preparation of cis- and trans-4-fluoro-5-pyrrolidone-2-carboxylic acids (4-fluoropyroglutamic acids)

Separation of the 4-fluoroglutamic acid diastereomers has been achieved by crystallizationof the hydrochlorides of their dialkyl esters 1b and 2d. Subsequent hydrolysis affordedthe diastereomers 1a and 2a in 100% steric purity. Conversion of the acids into the 5-methyl esters followed by treatment with ammonia gives rise to the trans and cis isomersof 4-fluoro-5-pyrrolidone-2-carboxylic acid, 3 and 4. NMR data are given.