Acetic Acid → DL-threo-beta-Hydroxyaspartic acid

Participants

Reaction Conditions

Reaction Steps

(3S)-3-Hydroxyaspartic acid is prepared by the method of G. Cardillo, L. Gentilucci, A. Tolomelli, C. Tomasini, Synlett 1999, 1727-1730, and converted in analogy to P. G. Mattingly, M. J. Miller, J. Org. Chem. 1983, 48, 3556-3559, using microwave radiation in a closed reactor into (2S,3S)-2-amino-3-hydroxy-4-methoxy-4-oxobutyric acid hydrochloride. (2S,3S)-2-Amino-3-hydroxy-4-methoxy-4-oxobutyric acid hydrochloride (447 mg, 2.24 mmol) is dissolved in DMF (9 ml). The solution is cooled to 0° C., Boc-glycin-N-hydroxysuccinimide ester (763 mg, 2.91 mmol, 1.3 equivalents), DMAP (14 mg, 0.11 mmol, 0.05 equivalents) and finally DIPEA (1170 μl, 6.72 mmol, 3 equivalents) are added. The mixture is allowed to warm slowly to room temperature and is then stirred for 2 h. The mixture is acidified with glacial acetic acid, mixed with acetonitrile and chromatographed on Sephadex LH 20 (method 45). Product-containing fractions are combined, concentrated and again chromatographed (method 46). The obtained product (761 mg, quant.) is reacted further without further purification. For analytical purposes, a pure sample is obtained by HPLC (method 44).

Provenance & Evidence