Preparation of pregabalin and related compounds

A method of making a compound of Formula 9,

• or a pharmaceutically acceptable complex, salt, solvate or hydrate thereof, the method comprising:
• (a) reducing a cyano moiety of a compound of Formula 16,
• or a salt thereof, to yield the compound of Formula 9 or a salt thereof;
• (b) optionally converting the compound of Formula 9 or a salt thereof into a pharmaceutically acceptable complex, salt, solvate or hydrate;
• (c) wherein the compound of Formula 16 is prepared by decarboxylating a compound of Formula 11,
• or a salt thereof;
• (d) wherein the compound of Formula 11 is prepared by contacting a compound of Formula 12,
• with an enzyme to yield the compound of Formula 11 and said enzyme is adapted to enantioselectively hydrolyze the compound of Formula 12 to the compound of Formula 11, or a salt thereof;
• R3 in Formula 11 and 12 are each independently represented by C1-12 alkyl, C3-12 cycloalkyl, or aryl-C1-6 alky,
• R4 in Formula 12 is represented by C1-12 alkyl, C3-12 cycloalkyl, or aryl-C1-6 alky, and;
• R5 in Formula 16 is represented by hydrogen, C1-12 alkyl, C3-12 cycloalkyl, or aryl-C1-6 alkyl.