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 14,
• or a salt thereof, to yield a compound of Formula 15,
• or a salt thereof;
• (b) decarboxylating the compound of Formula 15 or a salt thereof to yield the compound of Formula 9, or a salt thereof;
• (c) optionally converting the compound of Formula 9 or a salt thereof into a pharmaceutically acceptable complex, salt, solvate or hydrate;
• (d) wherein the compound of Formula 14 is prepared by hydrolyzing a compound of Formula 11
• or a salt thereof, in which R3 is represented by C1-12 alkyl, C3-12 cycloalkyl, or aryl-C1-6 alkyl, and;
• (e) the compound of formula 11 is prepared by a method further comprising:
• contacting a compound of Formula 12,
• with an enzyme to yield the compound of Formula 11 and a compound of Formula 13
• wherein the enzyme is adapted to enantioselectively hydrolyze the compound of Formula 12 to the compound of Formula 11 or a salt thereof;
• R3 in Formula 12 and Formula 13 is as defined in Formula 11;
• and
• R4 in Formula 12 and Formula 13 is the same as or different than R3 and is C1-12 alkyl, C3-12 cycloalkyl, or aryl-C1-6 alkyl.