Synthetic processes for the preparation of aminocyclohexyl ether compounds

A method of making a compound of formula (I):

• or a pharmaceutically acceptable salt thereof, as a single stereoisomer or as a mixture thereof;
• wherein:
• R3, R4 and R5 are independently bromine, chlorine, fluorine, carboxy, hydrogen, hydroxy, hydroxymethyl, methanesulfonamido, nitro, cyano, sulfamyl, trifluoromethyl, —CHF2, —SO2N(R8)R9, —OCF3, C2-C7alkanoyloxy, C1-C6alkyl, C1-C6alkoxy, C7-C12aralkoxy, C2-C7alkoxycarbonyl, C1-C6thioalkyl, aryl or —N(R6)R7;
• and
• R6, R7, R8, and R9 are each independently selected from hydrogen, acetyl, methanesulfonyl or C1-C6alkyl;
• which method comprises:
• a) a nucleophilic displacement step comprising treating a compound of formula (16):
• wherein —OR′ is an activated leaving group and R3, R4 and R5 are as defined above, with an azide under suitable nucleophilic displacement conditions and subsequent reduction conditions to form a compound of formula (17):
• wherein R3, R4 and R5 are as defined above;
• b) reacting the compound of formula (17):
• wherein R3, R4 and R5 are as defined above, with a compound of formula (2a2):
• wherein R is H, C2-C5acyl or an oxygen-protecting group, under suitable condensation conditions to form a compound of formula (6b):
• wherein R is H, C2-C5acyl or an oxygen-protecting group and R3, R4 and R5 are as defined above;
• and
• c) reducing the compound of formula (6b) under suitable conditions to form a compound of formula (I), as set forth above;
• and
• d) optionally forming the pharmaceutically acceptable salt of the compound of formula (I) under suitable conditions.