合成路线1

Stereoselective Synthesis of BAY X 1005: To prepare larger amounts of BAY X 1005 a second order stereoselective synthesis was elaborated: The starting material [4-(2-quinolinylmethoxy)phenyl]acetic acid (X) is esterified with D-menthol and toluene sulfonic acid in boiling toluene. Following alkylation with cyclopentylbromide and excess potassium tert-butylate in DMF leads to a diastereomeric mixture. Under the reaction conditions the diastereomer (XII) precipitates, whereas the remaining soluble diastereomer undergoes continuous epimerization. After crystallization a yield of > 85% of the desired diastereomer (XII) results with a de > 99%. Acidic cleavage with sulfuric acid yields the (R)-(-)-enantiomer BAY X 1005.