This document provides two methods for synthesizing phenylcyclohexylpiperidine or analogs from readily available starting materials. Method 1 involves reacting cyclohexanone with ethylamine to form an intermediate, which is then reacted with phenyllithium. Method 2 involves reacting cyclohexylamine and piperidine to form a cyclohexenyl-piperidine intermediate, which is then reacted with benzyl magnesium bromide. Both methods conclude by converting the free base product to its hydrochloride salt for isolation.
This document provides two methods for synthesizing phenylcyclohexylpiperidine or analogs from readily available starting materials. Method 1 involves reacting cyclohexanone with ethylamine to form an intermediate, which is then reacted with phenyllithium. Method 2 involves reacting cyclohexylamine and piperidine to form a cyclohexenyl-piperidine intermediate, which is then reacted with benzyl magnesium bromide. Both methods conclude by converting the free base product to its hydrochloride salt for isolation.
This document provides two methods for synthesizing phenylcyclohexylpiperidine or analogs from readily available starting materials. Method 1 involves reacting cyclohexanone with ethylamine to form an intermediate, which is then reacted with phenyllithium. Method 2 involves reacting cyclohexylamine and piperidine to form a cyclohexenyl-piperidine intermediate, which is then reacted with benzyl magnesium bromide. Both methods conclude by converting the free base product to its hydrochloride salt for isolation.
This document provides two methods for synthesizing phenylcyclohexylpiperidine or analogs from readily available starting materials. Method 1 involves reacting cyclohexanone with ethylamine to form an intermediate, which is then reacted with phenyllithium. Method 2 involves reacting cyclohexylamine and piperidine to form a cyclohexenyl-piperidine intermediate, which is then reacted with benzyl magnesium bromide. Both methods conclude by converting the free base product to its hydrochloride salt for isolation.
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"METHOD 1. A mixture of 100 g of anhydrous ethylamine and 220 g of cyclohexanone is kept 16 hours, shaken with solid KOH, and the oil layer is removed by decantation. Distill the oil layer in vacuo to get the intermediate N-cyclohexylidenethylamine. Prepare a mixture of phenyllithium by mixing 11 g of lithium and 76 ml PhBr in 500 ml of Et20. Add the phenyllithium dropwise to a solution of 51 g of the N-cyclohexylidenethylamine in 500 ml of Et20, with stirring and cooling, to keep the temp at 0�. Stir for one hour and then decompose by adding water. Separate the Et20 layer, wash with H20 and distill to get 1-phenylcyclohexylethylamine or analog. The hydrochloride form is obtained in the usual way, as given below. METHOD 2. A mixture of 170 g of piperidine, 220 g of cyclohexylamine, and 750 ml of benzene is azeotropically distilled until the evolution of H20 stops, then vacuum distill to get cyclohexenyl-piperidine. p-toluenesulfonic acid monohydrate (190 g) in 250 ml of PhMe is heated under a water trap until all the H20 is removed, then add a solution of 165 g of cyclohexyl-piperidine in 500 ml of Et20, with cooling, to keep temp at 0�. A solution of I mole of PhMgBr (made from 157 g of PhBr and 24 g of Mg) in 750 ml of Et20 is added (still holding the temp at 0� to 5�). The mixture is stirred for an additional 30 min after the dropwise addition is complete. Decompose the mixture by adding an excess saturated NH4Cl and NH40H. The Et20 layer is removed, dried over K2CO3, and distilled to give phenylcyclohexylpiperidine. Convert to the hydrochloride form by dissolving the free base in an excess of iso-PrOH-HC1 and then precipitate the salt (the hydrochloride) with Et20 and crystallize from Et20-iso-PrOH (this is a mixture). "
