Efficient one-pot synthesis of the GABA(B) positive allosteric modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one

摘要

The GABA(B) positive allosteric modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (1) was synthesized in one pot from the anhydrous lithium salt of 2,4-di-tert-butylphenol and methyl trifluoropyruvate mediated by a stoichiometric amount of anhydrous gallium(III) chloride in 64% overall yield. The enantiomers of 1 were separated by chiral-phase HPLC (Chiralpak AD (R)), and the absolute configuration was determined by X-ray crystallography.