Patent ID: 8426610

Claim:
A process for preparing asenapine of formula A, or a salt thereof, from a mixture of isomers without the use of post reaction isomer separation techniques the process comprising: (a) Stereoselectively preparing a trans-amino acid derivative which is Formula I, Formula II, or a mixture of Formula I and Formula II: or a salt thereof, by reacting with a base in the presence of an alcohol a lactam mixture which is: (i) a mixture of lactams of Formula IV and Formula V: (ii) a mixture of lactams of Formula VII and Formula VIII: (iii) a mixture of the mixtures of lactams of (i) and (ii), said reaction thereby stereoselectively opening the trans isomer in said mixture, and isolating said trans-amino acid derivative product from the reaction mixture by: (A) neutralization of the reaction mixture; or (B) treating the corresponding hydrochloride salt of the ring-opened product with ammonia or sodium hydroxide solution; (b) cyclizing said ring-opened products isolated from Step (a) thereby yielding: (1) the lactam of Formula IV if the lactam mixture used in Step (a) was a mixture of Formula IV and Formula V: (2) the lactam of Formula VII if the lactam mixture used in Step (a) was a mixture of Formula VII and Formula VIII; or (3) a mixture of lactams of Formula VII and IV if the lactam mixture (iii) was provided in Step (a); (c) reducing the carbonyl moiety of the lactam or lactam mixture prepared in Step (b) to give the compound of Formula A; and (d) optionally converting the compound of Formula A from step (c) to a salt.