4-Toluenesulfonyl chloride → (R)-N-(2-(3,3-Diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester

Participants

Reaction Steps

A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (2.5 g, 0.010 mol) in dry THF (20 ml) was placed on an ice-bath and a solution of n-butyllithium in hexanes (4.0 ml, 2.5 M) was added dropwise under an atmosphere of nitrogen. When addition was complete the reaction mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 1 h. The mixture was cooled to room temperature and p-toluenesulphonyl chloride (2.1 g, 0.011 mol) was added. The mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 1 h. To the cooled reaction mixture was added dry potassium carbonate (2.0 g, 0.015 mol) and ethyl (R)-3-piperidinecarboxylate (2.0 g, 0.0125 mol) and the mixture was heated at reflux temperature for 3 h. The cooled reaction mixture was poured into water (200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic extracts was dried over sodium sulphate and the solvent evaporated in vacuo. The residue was submitted to flash chromatography on silica gel (150 g) using a mixture of n-heptane and THF (4:1) as eluent. This provided 0.9 g (11% calculated from 3,3-diphenyl-1-propanol) of the title compound as an oil. TLC: rf=0.24 (SiO2 ; n-heptane/THF=7:3). 1H NMR δ (CDCl3) 4.10 (t, 1H).

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