Cyclohexanone → HCID 23312313, compound

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Reaction Steps

480 ml of a 1.35N solution of n-butyl lithium in abs. diethyl ether is added dropwise within 30 minutes at -5° to a solution of 60 g of 1-methyl-4-(5-bromo-2-benzofuranyl)-piperidine [cp. Example 19] in 300 ml of diethyl ether. The reaction temperature during the dropwise addition is maintained at between -5° and 0° by external cooling. The solution is afterwards stirred for a further 90 minutes at 5° to 10°. There is then added dropwise within 30 minutes a solution of 85 ml of cyclohexanone in 100 ml of abs. diethyl ether, with the reaction temperature being kept at 0° to 5° by external cooling. The reaction solution is subsequently stirred for 15 hours at room temperature, and then poured, with stirring, onto 300 g of ice, and the aqueous phase extracted three times with 500 ml of ethyl acetate each time. The combined organic extracts are dried over sodium sulphate, filtered, and concentrated by evaporation. The residue is dissolved in 300 ml of 2N hydrochloric acid, and the acid solution washed with ether. The aqueous solution is then adjusted by addition of 10% sodium hydroxide solution to pH 12, and extracted with 1000 ml of chloroform. The chloroform solution is dried with sodium sulphate, filtered off, and concentrated by evaporation to obtain crude 1-methyl-4-[5-(1-hydroxycyclohexyl)-2-benzofuranyl]-piperidine. The free base melts at 155° to 157° after recrystallisation from cyclohexane. The hydrochloride is prepared with hydrogen chloride in ethyl acetate, and recrystallised from acetone, whereupon it melts at 226°-229°.

Provenance & Evidence