Synthesis
1) Preparation of Boc-Asn(Me)-OBzl: Dissolve Boc-Asp-OBzl in tetrahydrofuran, add 1.5 molar amounts of HOSu (based on the molar amount of Boc-Asp-Obzl, the same below), add 1.2 molar amounts of DCC dropwise, and cool to 2℃; add 2 molar amounts of methylamine tetrahydrofuran solution dropwise into the reaction solution; react for 2 hours; add a small amount of water to the reaction solution, filter DCC, rotary evaporate tetrahydrofuran, dissolve in ethyl acetate, filter the insoluble matter, wash with dilute acid, wash with water, wash with sodium bicarbonate solution, wash with water, dry, and evaporate to dryness to obtain Boc-Asn(Me)-OBzl.
2) Preparation of 1-methyl-L-4,5-dihydroorotic acid: Boc-Asn(Me)-OBzl was dissolved in ethanol, sodium ethoxide was added, the mixture was refluxed for 4 hours, cooled and neutralized with dilute hydrochloric acid, the ethanol was distilled under reduced pressure, the mixture was washed with petroleum ether, the aqueous layer was extracted with ethyl acetate, the ethyl acetate layer was washed with saturated brine, the ethyl acetate was dried over anhydrous magnesium sulfate, filtered, and rotary evaporated to obtain 3-methyl-L-4,5-dihydroorotic acid benzyl ester; 3-methyl-L-4,5-dihydroorotic acid benzyl ester was dissolved in methanol, and hydrogenolyzed by 5% Pb-C catalyst at room temperature overnight, the catalyst was filtered, and the methanol was evaporated to obtain 1-methyl-L-4,5-dihydroorotic acid solid.
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