Taro Pharmaceutical Industries Limited

Sorin Bercovici

Konstantin Ulanenko

Daniella Gutman

Shimon Chernyak

Wael Baidossi

Simon Cherniak

Osvaldo Fuxman

Mirela Jakoel

Sbar Sasson

Robert Graff

Yuval Evron

Michel Ashkar

The present invention is related to a novel synthetic procedure that provides a simple, safe and commercially valuable method for the preparation of 2-phenyl-1,3-propanediol. The process for the preparation of 2-phenyl-1,3-propanediol involves reducing diethyl phenylmalonate with sodium borohydride (NaBH) in the presence of an alkali metal dihydrogen phosphate buffer or the hydrate thereof.

Process for the preparation of 2-phenyl-1,3-propanediol

The invention provides a method for the direct preparation of pure warfarin sodium from warfarin acid. The reaction is conducted in a polar organic solvent, preferably ethanol, using a volatilizable base, preferably sodium bicarbonate or sodium carbonate, at low temperature. Drying the final product is accomplished at low temperature to avoid decomposition of the final warfarin sodium product.

Preparation of warfarin sodium from warfarin acid

The present invention is a method for producing warfarin sodium from warfarin sodium 2-propanol clathrate by thermal, nondestructive solvent expulsion. The solvent expulsion is conducted under conditions of controlled heat transfer whereby the 2-propanol is expelled from the warfarin sodium 2-propanol clathrate without decomposition of warfarin sodium or the clathrate. Heating is conducted the clathrate at a temperature from about 100&deg; C. to about 170&deg; C. in an active oven under air or in an inert atmosphere and at partial pressures ranging from that of a relative vacuum to atmospheric pressure. The invention also relates to pure warfarin sodium prepared according to the method of the invention and pharmaceutical compositions containing warfarin sodium.

Preparation of warfarin sodium from warfarin sodium-2-propanol clathrate by solvent expulsion

An improved procedure for the purification of warfarin acid. Sodium, potassium and lithium warfarin salts and the corresponding clathrates are prepared in high, pharnacopeial grade purity and good yields from the pure warfarin acid and the respective metal salt bases in suitable media.

Process for synthesis of pure warfarin acid, warfarin alkali metal salts and corresponding clathrates

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Sorin Bercovici