THE NEW PROCESS FOR THE PREPARATION OF (+)-DULOXETINE HCL VIA (S)-3-METHYL-6-(2-THIENYL)-1,3-OXAZINAN-2-ONE

摘要

PURPOSE: A novel method for preparing (+)-duloxetine HCl, (S)-(+)N-methyl-3-(1-naphthalenyl oxy)-3-(2-thienyl)propaneamine hydrochloride, is provided to effectively and economically obtain (+)-duloxetine HCl with high yield and high purity. CONSTITUTION: A method for preparing (S)-(+)N-methyl-3-(1-naphthalenyl oxy)-3-(2-thienyl)propaneamine hydrochloride((+)-duloxetine HCl) denoted by structural formula 1 comprises: a step of reacting (S)-3-N,N-dimethyl-3-hydroxy-3-(2-thienyl)-propane amine denoted by structural formula 3 with phenyl chloroformate in toluene under the presence of triethyl amine, to preparing phenyl(S)-N-[3-phenyloxycarbonyl oxy-3-(2-thienyl)propyl]-N-methyl carbamate denoted by structural formula 4; a step of reacting the compound denoted by the structural formula 4 with a base in an alcohol solvent to prepare (S)-3-methyl-6-(2-thienyl)-1,3-oxaxinan-2-one denoted by structural formula 2; and a step of adding potassium hydroxide in a mixture solvent of dimethyl sulfoxide and toluene. The alcohol solvent is methanol. The base is potassium hydroxide.