Zentiva K.s.

Monika Zatopkova

Ludek Ridvan

Lukas Placek

Kamal Jarrah

Tomas Pekarek

Stanislav Radl

Josef Cinibulk

Michal Voslar

Lucie Krumbholcova

A method for the preparation of a duloxetine hydrochloride salt from a duloxetine base, comprising the steps of: reacting duloxetine base with concentrated hydrochloric acid in ethylmethylketone; and crystallizing duloxetine hydrochloride salt from said concentrated hydrochloric acid in ethylmethylketone.

Method for the preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine)

In the preparation of zolmitriptan of formula III the reduction of the diazonium salt to (5)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one of formula IV is performed in a more concentrated mixture and by the effect on an alkali metal disulphite, preferably sodium disulphite. A zolmitriptan toluene solvate, characterized by a toluene content of 9 to 14% by weight according to the gas chromatography determination and by a maximum of the corresponding mass loss at temperatures of about 111&#xb0; C. in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm1, characteristic for toluene. 

Method for the preparation of zolmitriptan

A method of preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-mienyl)propylamine of Formula (I) and its pharmaceutically acceptable salts, comprising a) reaction of (RS)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with optically active D-tartaric acid or an acid salt derived from D-tartaric acid forming a mixture of diastereoisomeric salts of N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine and D-tartaric acid (2:1), b) isolation of the salt (S)-N,N-dimethyl-3-(naphthyloxy) -3-(2-thienyl)propylamine/D-tartrate (2:1) from the mixture of diastereoisomeric salts in an organic solvent, water or a mixture thereof and release of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an inorganic or organic base, c) demethylation of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an alkylchloroformate of formula ClCOOR (R=C-Calkyl, or C-Caryl or alkylraryl), especially phenyl, ethyl or methyl chloroformate, and d) hydrolytic release of the duloxetine base of formula I and optionally conversion of the base to a salt with the respective acid, or salt of a weak base. 

[object Object]

Growing community of inventors

Ostrava, Czechia

Monika Zatopkova