Preparation of pregabalin and related compounds

1. 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 R 3 is represented by C 1-12 alkyl, C 3-12 cycloalkyl, or aryl-C 1-6 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;

R 3 in Formula 12 and Formula 13 is as defined in Formula 11; and

R 4 in Formula 12 and Formula 13 is the same as or different than R 3 and is C 1-12 alkyl, C 3-12 cycloalkyl, or aryl-C 1-6 alkyl.