ChemicalBook CAS DataBase List (±)-Duloxetine

(±)-Duloxetine synthesis

10synthesis methods

Product Name:(±)-Duloxetine
CAS Number:116817-13-1
Molecular formula:C18H19NOS
Molecular Weight:297.41

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Yield:116817-13-1 93.8%

Reaction Conditions:

with potassium hydroxide in dimethyl sulfoxide at 105; for 2 h;

Steps:

5

The mother lye obtained in the crystallization process of Example 4 is mixed with 30 ml of 10 percent by weight aqueous sodium hydroxide solution with cooling, the diethylether phase is dried over magnesium sulphate and evaporated to dryness.Yield, 6.5 g yellow oil containing approx. 70.5 percent by weight (-)-N-methyl-3-(l-naphtyloxy)-3-(2-thienyl)-propilamine free base according to HPLC analysis. The oil is mixed with 30 ml of dimethylsulphoxide and 1.0 g potassium hydroxide and the mixture is heated for two hours at the temperature of 105 ⁰C with stirring. The suspension is poured onto the mixture of 50 g of ice and 50 ml of toluene, the phases are separated, the toluene layer is dried and evaporated to dryness.Yield, 6.1 g (93.8 %) yellow oil, which is duloxetine free base racemate according to HPLC analysis. Example 6(+)-N-methyl-3 -(I -naphtyloxy)-3 -(2-thienyl)-propylamine hydrochloride (1:1)A vessel equipped with high-speed stirrer is charged with 200 ml of 2- propanol, 10.0 g (33.3 rnmol) duloxetine free base and under intensive stirring, 50 ml of 2-propanol containing 10% hydrochloric acid are added dropwise. The solution is boiled for a few minutes, decolorized, the product precipitated upon cooling is collected at the temperature of 0 ⁰C, washed with ethylacetate and dried.Yield, 14.2 g (85.2 %) white crystalline solid.Elemental analysis [calculated on the basis of the Formula Ci₈H₁₉NOS HCl (333.9)]:Calculated C: 64.75 H:6.04 N:4.20 S:9.60Measured C: 64.62 H:5.98 N:4.32 S:9.54Enantiomer purity: 99.7 %.The amount of the impurity of (+/-)-N-methyl-3-(2-thienyl)-3-(4- hydroxy-l-naphtyl)-propylamine of the Formula (II) in the thus obtained product is approximately 0.05 percent by weight as determined by HPLC.

References:

WO2007/105021,2007,A2 Location in patent:Page/Page column 27