(WO/2007/119118) SYNTHESIS AND PREPARATIONS OF INTERMEDIATES AND POLYMORPHS THEREOF USEFUL FOR THE PREPARATION OF DONEPEZIL HYDROCHLORIDEThis application claims priority to United States Provisional Application No. 60/735,838, filed November 14, 2005, which is expressly incorporated herein by reference in its entirety.The invention relates to an improved process for preparing 2-(l-benzylpiperidin-4- ylmethyliden)-5,6-dirnethoxyindan-l-one (a key intermediate in the synthesis of donepezil hydrochloride), crystalline polymorph forms of this key intermediate and their use thereof for producing donepezil hydrochloride. 2. Discussion of the Related Art5,6-Dimethoxyindan-l-one (30.0 g), l-benzylpiperidine-4-carbaldehyde (35.2 g), potassium hydroxide (6.81 g) and benzyltriethylammonium chloride (1.78 g) were suspended in a mixture of toluene (190 mL) and water (20 mL) at room temperature. Nitrogen was bubbled through the suspension for 30 minutes, and the mixture was then heated to reflux temperature. After stirring at reflux temperature for 8 hours, water was added (190 mL), and the toluene was removed from the reaction mixture by distillation. The mixture was then cooled to 20-25° C, and the resulting crystals were isolated by filtration to yield 72.2 g of Compound 1. (Yield: Quantitative; Loss on Drying: 19.0%, 58.5 g).
DONEPEZIL POLYMORPH
donepezil for dementia due to
