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A five-step sequence allowing the preparation of ethyl 3-aminopropanedithioate from N -(Boc)-b -alanine via the key intermediate N -(Boc)-b -alaninethioacyl-N -phthalimide is described.Esters of dithiocarboxylic acids are versatile tools in organic synthesis. 1,2 Their traditional precursors are dithioacid salts and thioacyl halides, the related thioacids are prepared by the reaction of carbon disulfide either with organometallic reagents and nucleophilic carbanions, or with aromatic compounds under FriedelÐCrafts conditions. 3,4 Thiohydrolysis of imidothiolates prepared from nitrile-or thioamide precursors constitutes another valuable method of dithioesters synthesis. 3,4 Lastly, thionation of thioesters has been achieved by the use of Lawesson's reagent 4 . 5,6 The previous methods can be readily applied to the simple cases of aromatic and non-functionalized aliphatic compounds. On the other hand, the preparation of aminodithioester derivatives appeared somewhat more difficult. Amino nitriles are the usual precursors 7Ð9 and, recently, a modified procedure of the Pinner reaction has also been proposed. 10 In the course of the total synthesis of a drug precursor, we required the b -alanine dithioester building block. We tried to prepare the N -protected compound using the classical methods, i.e. a) by the reaction of 2-( N -phthalimido)aminobromoethane with magnesium, followed by CS 2 and MeI and b) by the reaction of ethyl 3-( N -tert -butoxycarbonyl)aminopropanethioate (2) with Lawesson's reagent 4 (Scheme 1). The first route failed. The second one gave only poor yields of the required dithioester 3 , probably as a result of the lack of selectivity of the thionation reagent 4 towards the thioester carbonyl versus the carbamate function. Therefore, we decided to consider the primary amide 5 as the starting material (Scheme 2). The selective thionation of primary carboxamides in the presence of carbamate protecting groups has been well established. 11,12 N -(Boc)-b -alanine (1) was activated with 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) in the presence of ammonium bicarbonate 13 to furnish the corresponding amide 5 , which was purified by crystallization. Scheme 1 Scheme 2Downloaded by: University of Liverpool. Copyrighted material.

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