合成路线1

Two related syntheses of a known intermediate of carumonam are presented: 1) The reaction of calcium L-threonate (I) with HBr in acetic acid - acetic anhydride and then with refluxing methanol gives methyl (2S,3S)-2,4-dibromo-3-hydroxybutanoate (II), which by reaction with concentrated NH4OH is converted into (2S, 3R)-3-(bromomethyl)oxiranecarboxamide (III). The reaction of (III) with KI and potassium acetate in hot DMF affords (2R, 3S)-3-(acetoxymethyl)oxiranecarboxamide (IV), which is treated with concentrated NH4OH at 60 C and then with benzyl chloroformate (V) to give (2S, 3R)-2-(benzyloxycarbonylamino)-3,4-dihydroxybutanamide (VIII), an intermediate compound previously obtained in the synthesis described in Drugs Fut 1985, 10: 967. 2) The treatment of dibromide (II) with KI and potassium acetate in hot DMF gives methyl (2S,3S)-4-acetoxy-2,3-epoxybutanoate (VI), which is treated first with NaOH in methanol and then with hot NH4OH to yield (2S, 3R)-2-amino-3,4-dihydroxybutanamide (VII). Finally, this compound is treated with benzyl chloroformate (V) as before to give the intermediate (VIII) previously mentioned.