| 摘要 |
A preparation method of optically active benzoxazine derivatives is provided to simplify the preparation procedures by eliminating the chromatography process, and improve optical purity by using (L)-alaninol as a natural amino acid, so that the method is useful for industrial production of the compounds. A preparation method of optically active benzoxazine derivatives represented by the formula(1) comprises the steps of: (a) adding trimethyl orthoformate into 2,3,4,5-tetrafluorobenzoylacetic acid ethyl represented by the formula(10) to prepare compounds represented by the formula(11); (b) substituting the compounds represented by the formula(11) by L-alaninol to prepare compounds represented by the formula(12); (c) cyclizing the compounds represented by the formula(12) in the presence of polar solvent and base to prepare intermediate compounds represented by the formula(13) and the formula(8); (d) reacting the intermediate compounds represented by the formula(13) and the formula(8) in the presence of polar solvent and base to prepare compounds represented by the formula(9); and (e) reacting the compounds represented by the formula(9) with C1-C6 4-alkyl-piperazine in the presence of polar solvent and base, wherein the polar solvent is methanol, ethanol, isopropanol, acetonitrile, tetrahydrofuran, N,N-dimethylformamide or dimethylsulfoxide; and the base of steps (c) and (d) is potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium hydroxide or a mixture thereof, and the base of step (e) is pyridine, triethylamine or imidazol.
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