Nobuhiro Fujii

Synthesis of TAK-218 using (R)-2-methylglycidyl tosylate as a chiral building block

Abstract We performed an asymmetric synthesis of ( S )-2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)methyl]-5-benzofuranamine dihydrochloride (TAK-218, 1 ), a compound used for the treatment of traumatic and ischemic central nervous system injuries. Oxirane 6 , which was synthesized from ( R )-2-methylglycidyl tosylate, was treated with aqueous trifluoroacetic acid to afford benzofuranmethanol 7 with inversion of stereochemistry at the stereogenic center. Compound 7 was converted into 1 with high enantiomeric excess in four steps.