Acetonitrile → (2R,4S)-methyl 4-acetamido-2-(4-chlorobenzyl)piperidine-1-carboxylate

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Reaction Steps

At -40° C., 20.6 ml (308 mmol) of chlorosulfonic acid are introduced into 500 ml of acetonitrile. A solution of 48.0 g (154 mmol) of N-[1-(4-chloro-benzyl)-but-3-enyl]-N-ethoxymethyl-carbamic acid methyl ester in 50 ml of acetonitrile is added dropwise in such a manner that the reaction temperature does not exceed -10° C. The mixture is then stirred for 20 minutes at -15° C. before 370 ml of 2 N sodium hydroxide solution and 100 ml of 10% aqueous sodium hydrogen carbonate solution are added to the reaction. The phases are separated and the aqueous phase is then extracted twice with toluene. The combined organic phases are dried over sodium sulfate. The crude product is crystallised from toluene and yields the title compound in the form of white crystals. M.p.: 169-170° C. TLC: methylene chloride/methanol/conc. ammonia (90:9:1) Rf =0.42, FD-MS: M+ =325.

Provenance & Evidence