PROCESS FOR THE PREPARATION OF DULOXETINE AND FOR THEIR THE INTERMEDIATES

• Main Authors: TEMESVARI KRISZTINA, FOGASSY ELEMER DR, SCHINDLER JOZSEF, BODI JOZSEF DR, SZOEKE KATALIN, VUKICS KRISZTINA, GATI TAMAS DR, ELES JANOS DR, FARAGO JANOS
• Format: Patent
• Language: English
• Published: 30.01.2012
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

The present invention relates to a process for the preparation of duloxetin. ((S)-(+)-N-methyl-N-(3-(l-na?hthalenyloxy)-3-(2-thienyl)propanamine) of formula (I) and pharmaceutically acceptable salts thereof, said process comprising the steps of a) resolving racemic 3-(N-methyl-N-berizylamino)-1-(2-thienyl)-1-propanol of formula (II) with a D-phenylglycine derivative to obtain a compound of formula (IV); and b) reacting (S)-3-(N-methyl-N-ben2yIamino)-1-(2-thienyl)-1-propanol of formula (IV) with 1-fluoronaphthalene to yield (S)-N-methyl-N-benzyl-3-(1-naphthalenyloxy)-3-(2- thienyl)propanamine of formula (V), reacting the compound of formula (V) obtained with 1-chloroethyl chloroformate to yield duloxetin of formula (I), and if desired converting the duloxetin of formula (I) obtained into an acid addition salt thereof.