Efficient synthesis of CCR5 antagonist, 2,3-dihydro-1-benzothiepine derivatives by improved intramolecular Claisen type reaction using dialkylcarbonate

The efficient synthesis of 2,3-dihydro-1-benzothiepine derivatives 4 has been developed. The intramolecular Claisen type reaction of the new products, 4-(o-formylphenylthio)butyrate 9, with alcoholate in dialkylcarbonate as a solvent afforded 4 in good yields. According to this new procedure, we have accomplished the practical preparation of CCR5 antagonist 1 as a candidate for oral HIV-1 therapy.