Benzyl chloroformate → 4-Amino-1-Cbz-piperidine-4-carboxylic acid

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Reaction Conditions

Reaction Steps

4-amino-4-carboxy-piperidine hydrobromide ([P. Jacobsen, K. Schaumburg, P. Krogsgaard-Larsen, Acta. Chem. Scandinavica B34, 319-326 (1980)]; 2.25 g, 10 mmoles) was dissolved in a solution of 18 ml potassium dihydrogen phosphate buffer (0.05 Molar potassium dihydrogen phosphate in 1N aqueous sodium hydroxide) and 6 ml of water. The solution was chilled with an ice-bath over an hour period during which solutions of carbobenzyloxy chloride (1.57 ml, 11 mmoles) in 3.0 ml of toluene and aqueous 1N sodium hydroxide were simultaneously added dropwise so as to maintain a pH of 7.0. The mixture was then stirred for one hour at 5° C., and for four additional hours at ambient temperature. The precipitate formed during the reaction was filtered and the filter cake washed with 3 (30 ml) portions of diethyl ether. The amorphous colorless solid was dried in vacuo affording 1.4 g of the title compound (50% yield). 1Hnmr (60 mHz; CF 3 CO2D) delta 2.0-2.7 (4H, broad m), 3.5-4.5 (4H, broad m), 5.28 (2H, s), 7.4 (5H, s).

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