The invention discloses a novel preparation method of netaglinide
oxazolone shown in the formula (IV), which comprises the following steps: under the action of a catalyst A, enabling 3-
fluorine-4-
morpholine phenyl isocyanate shown in the formula (I) to react with (R)-
epoxy chloropropane to obtain a compound (II), wherein the catalyst A is
magnesium diiodide,
magnesium dibromide,
magnesium dichloride,
magnesium perchlorate or magnesium trifluoromethanesulfonic acid; enabling the compound (II) to react with
sodium azide to obtain a compound (III); reducing the compound (III) by hydrogenation, and then, acetylating the reduced compound (III) to obtain the compound (IV). In the invention, the low-cost and environment-friendly catalyst (Lewis acid magnesium) is used for catalyzing the
cycloaddition reaction of the (R)-
epoxy compound and the
isocyanate to establish a mother
nucleus structure of the netaglinide
oxazolone by one step, thus the prepared netaglinide
oxazolone has high
stereoselectivity, does not need rigorous operation conditions, such as low temperature, no water, no
oxygen and the like, has the advantages of moderate
reaction conditions, simple and convenient operation, high utilization ratio of atoms, environment protection, low production cost and the like, and is suitable for industrialized production.