Oxaflumazine disuccinate

Chamical Nama N-3-(2-Trifiuoromethyl-10-phenothia2inyl)-propyl-N -2-[2-(1,3-dioxanyl)]-ethyl-piperazine disuccinate 

N-[2-(3,1 -DioxanyDethyl] piperazine 1 -Bromo-3-chloropropane 2-Trifluoromethylphenothiazine Sodium Succinic acid 

Preparation of N-(3-chlorQpropyl)-N -[2-(1,3-dioxanyl)-ethyl]-piperazine A solution of 30 g 

The sodium derivative of the 2-trifluoromethylphenothiazine was prepared from 26.7 g (0.1 mol) of 2-trifluoromethylphenothiazine and 2.3 g (0.1 g atom) of sodium in 500 ml of liquid ammonia. After the reaction was completed, the ammonia was driven off and 500 ml of dry toluene were added. A solution of 25 g (0.09 mol) of N-(3-chloropropyl)-N -[2-(1,3-dioxanyl)-ethyl] -piperazine In 200 ml of toluene was added drop by drop to this solution which was then refluxed with stirring for 1B hours. After cooling, the precipitate which had formed was filtered and the filtrate was washed with water, dried and concentrated in vacuo. 33 g of brown oil, the N-3-(2-trifluoromethyl-10-phenothiazinyl)-propyl-N -2-[2-(1,3-dioxanyl)] -ethyl-piperazine, were obtained. 

A warm solution of 4.4 g of the base obtained In 100 ml of acetonitrile was added to a warm solution of succinic acid in 200 ml of acetonitrile. After standing for 15 hours at 0°C, the crystalline product was obtained, melting point 13B°C. 

After filtration of the isopropylamine hydrochloride and bromohydrate, the solvent is stripped and the residue is admixed with 4N HCi and the aqueous phase is washed with ether. The aqueous phase is treated with 50% aqueous NaOH, the amine is ether-extracted and, after drying on anhydrous N82S04, the ether is distilled and the residue is rectified in vacuum to obtain 14 g of the product. Yield = 50%. 

The hydrochloride is crystallized by adding ethyl acetate to the base and then adding the necessary amount of pure alcohol saturated in dry HCI. Melting point 164 C. 

Mauvernay, R.Y., Busch, N., Moleyre, J. and Simond, J. U.S. Patent 3,637,680 January 25, 1972 assigned to Societe Anonyme Centre Europeen De Recherches Mauvernay 

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