Chloromethyl ethyl ether → Methyl (1-(4-chlorophenyl)pent-4-en-2-yl)(ethoxymethyl)carbamate

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Reaction Conditions

Reaction Steps

A suspension of 10.0 g of sodium hydride (80% in mineral oil, 333 mmol) in dry tetrahydrofuran [THF] is heated at reflux under argon. A solution of 60.5 g (238 mmol) of [1-(4-chloro-benzyl)-but-3-enyl]-carbamic acid methyl ester [McCarty F J, Rosenstock P D, Paolini J P, Micucci D D, Ashton L, Bennetts W W, J. Med. Chem, 1968, 11(3),534] in 50 ml of dry THF is added dropwise thereto in the course of 1 hour. The mixture is then boiled under reflux for 2 hours until the evolution of gas subsides. The mixture is cooled to 0° C. and chloromethyl ethyl ether is added dropwise in such a manner that the reaction temperature does not exceed 5° C. The mixture is then heated slowly to 25° C. and stirred for 12 hours to complete the reaction. Excess sodium hydride is destroyed carefully with 1 ml of water before more water is added. The phases are separated and the aqueous phase is extracted again with tert-butyl methyl ether. The combined organic phases are washed with brine, dried over sodium sulfate, and concentrated by evaporation. The crude product is distilled at 0.1 mbar and has a boiling range of 120-125° C. TLC: ethyl acetate/hexane (1:6) Rf =0.34, FD-MS: M+ =311 (313).

Provenance & Evidence