Methods of producing C-aryl glucoside SGLT2 inhibitors

A method of preparing a compound of Formula (I) or a pharmaceutically acceptable complex thereof

• wherein:
• R1 is selected from the group consisting of hydrogen, a hydroxy group, bromine, chlorine, fluorine, an alkyl group, an alkoxy group, an alkylthio group, and an arylthio group, where p is 1 to 4, and with the proviso that bromine, chlorine and fluorine, when present, are only present in at least one of the 3-, 4- and 5-positions;
• R2 is selected from the group consisting of hydrogen, a hydroxy group, chlorine, fluorine, an alkyl group, an alkoxy group, and an alkylthio group, where q is 1 to 5;
• and
• A is selected from the group consisting of a covalent bond, O, S, NH, and (CH2)n where n is 1 to 3, and
• with the proviso that when A is in the 4-position, R1 is not bromine;
• with the proviso that when one of R1 is bromine;
• and
• if A is in the 3- or 6-position, then bromine is in the 5-position,
• if A is in the 2- or 5-position, then bromine is in the 3-position, and
• when bromine is in the 3-position, and A is in the 2- or 5-position, then R1 groups in the 4- and 6-positions are the same and are not bromine, chlorine or fluorine, and
• when bromine is in the 5-position, and A is in the 3- or 6-position, then R1 groups in the 2- and 4-positions are the same and are not bromine, chlorine or fluorine, said method comprising:
• a) forming a compound of Formula (IV) from a lactone protected with an acid-labile protecting group
• wherein ALG is an acid labile protecting group,
• b) glycosidating of the compound of Formula (IV) in the presence of a nucleophilic compound which has an R3 group, with simultaneous removal of the acid-labile protecting group to form a compound of Formula (V);
• wherein R3 is selected from the group consisting of an alkoxy group, an alkenyloxy group, an alkylthio group and an alkenylthio group;
• c) reacting the compound of Formula (V) with an acylating agent to form a compound of Formula (VI);
• d) reducing the compound of Formula (VI) to provide a compound of Formula (VII);
• and
• e) removing acyl protecting group from the compound of Formula (VII) to provide a compound of Formula (I);
• wherein R1, R2, A, p and q are as defined hereinabove, and AC is an acyl protecting group.