Methylparaben → 4-(2-Piperidinoethoxy)benzoic acid hydrochloride

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To a 125 mL 3 neck flask with mechanical stirring, condensers, and a heating apparatus consisting of an RTD probe in the flask hooked via a temperature controller to a heating mantle, the following were added: 7.61 g methyl 4-hydroxybenzoate, 11.05 g -chloroethylpiperidine hydrochloride, 16.59 g powdered potassium carbonate, and 60 mL amyl acetate. The mixture was slowly heated under nitrogen in an oil bath to 97° C. The reaction was allowed to proceed overnight. The mixture was cooled to ambient temperature and 40 mL deionized water was added to dissolve the solids. The aqueous layer was separated and discarded and the water wash repeated. 25 mL of 8N hydrochloric acid were added in a single aliquot to extract the intermediate. The layers were separated and the acidic aqueous layer returned to the reaction flask. The aqueous layer was heated to 95° C. and the reaction was allowed to proceed for 24 hours as a stress test. After 6 hours, 0.3% of ester remained. The mixture was cooled to 40° C. and 25 mL acetone was added. The mixture was cooled to 0° C.-5° C. for 1 hour. The filter cakes were rinsed with approx. 25 mL acetone and dried. HPLC revealed 0.2 g of product in filtrate. Yield (crystalline) 13.38 g (95.1% of theoretical).

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