Process for the preparation of quetiapine fumarate

A process for the preparation of quetiapine or a pharmaceutically acceptable salt thereof, the process comprising the steps of:

• a) treating a compound of Formula III,
• with a halogenating agent to obtain a compound of Formula II;
• b) dissolving compound of Formula II in an aromatic hydrocarbon;
• c) optionally reducing the solvent by concentration;
• d) treating the resultant with hexane;
• e) recovering pure compound of Formula II;
• f) reacting the compound of Formula II or its salt thereof with piperazine in a mixture of solvent, which comprises an aromatic hydrocarbon and a polar aprotic solvent, to obtain a compound of Formula IV, or a salt thereof;
• g) alkylating a compound of Formula IV or its salt thereof;
• with 2-(2-chloroethoxy)ethanol of Formula V
• in a mixture of solvents, the mixture comprising either a mixture of an aromatic hydrocarbon and a polar aprotic solvent or a mixture of an aromatic hydrocarbon, water and a polar aprotic solvent, to obtain quetiapine wherein the alkylation is carried out in the absence of a phase transfer catalyst;
• h) treating quetiapine with a pharmaceutically acceptable acid;
• and
• i) isolating quetiapine or a pharmaceutically acceptable salt thereof.

A process for the preparation of quetiapine or a pharmaceutically acceptable salt thereof, the process comprising the steps of:

• a) treating a compound of Formula III,
• with a halogenating agent to obtain a compound of Formula II;
• b) dissolving the compound of Formula II in an aromatic hydrocarbon;
• c) optionally reducing the solvent by concentration;
• d) reacting the compound of Formula II or its salt thereof with piperazine in a mixture of solvents which comprises an aromatic hydrocarbon and a polar aprotic solvent, to obtain a compound of Formula IV, or a salt thereof,
• e) alkylating a compound of Formula IV, or its salt thereof;
• with 2-(2-chloroethoxy)ethanol of Formula V
• in a mixture of solvents, the mixture comprising either a mixture of an aromatic hydrocarbon and a polar aprotic solvent or a mixture of an aromatic hydrocarbon, water and a polar aprotic solvent, to obtain quetiapine, wherein the alkylation is carried out in the absence of a phase transfer catalyst,
• f) treating quetiapine with a pharmaceutically acceptable acid;
• and
• g) isolating quetiapine or a pharmaceutically acceptable salt thereof,
• wherein the entire process is carried out in-situ.