Synthesis of Diethyl (2S,3R)-2-azido-3-hydroxysuccinate from Diethyl (2R,3R)-2,3-epoxysuccinate -- DMAP as Catalyst
S. Saito, K. Komada, and T. Moriwake, Org. Synth, 73, 187, (1996)
A solution of DMAP (3.45 g, 0.0282 mol), dry DMF (17 mL), and dry ethanol (1.93 mL, 0.0329 mol) is stirred under a nitrogen aŽosphere and cooled in an ice-water bath. Azidothiomethylsilane (17.1 mL), 0.122 mol) is added dropwise by means of a syringe. A heterogeneous mixture is formed which is allowed to warm to ambient temperature.
Stirring is continued for a further 15 min. at ambient temperature and a solution of diethyl (2R,3R)-2,3-epoxysuccinate (17.7 g, 0.0940 mol) in dry chloroform (50 mL) is rapidly added. Stirring is continued until the epoxide can no longer be detected in the reaction mixture (TLC) (approximately 40 h).
Water (300 mL) is added, the organic phase separated, and the aqueous phase extracted with a hexane-ether mixture (1:1 v/v) (60 mL x 4). The combined organic phases are added to a stirred 2.3 N solution of hydrogen chloride in ethanol (20 mL). (This solution is prepared by carefully mixing acetyl chloride (3.28 mL) with ethanol to give a total volume of 20 mL). A further quantity of ethanol (50 mL) is added and stirring continued for a further 30 min. at ambient temperature. The reaction mixture is transferred to a separating funnel and successively washed with water (4 x 50 mL), saturated sodium bicarbonate solution (1 x 50 mL), and saturated brine (1 x 50 mL). The organic phase is dried over sodium sulfate, filtered, concentrated, and then exposed to high vacuum affording 96-98% pure diethyl (2S, 3R)-2-azido-3-hydroxysuccinate (18.6 g, 86%) as a pale yellow oil.
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