Preparation method of 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose

Abstract

The invention discloses a preparation method of 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose. The preparation method comprises the following steps of: (1) carrying out a hydrolysis reaction on 2,3-O-isopropylidene-5-deoxidization-D-furan glucoside and aqueous acid; (2) adding an acetylation reagent to the aqueous solution obtained in the step (1) to carry out an acetylation reaction, wherein the acetylation reagent is vinyl acetate or isopropenyl acetate; (3) post-treating the aqueous solution obtained in the step (2) to obtain a crude 1,2,3-tri-O-acetyl-5-deoxidization-D-ribose product; and (4) separating the crude product to obtain the 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose the purity of which is not lower than 99.5 percent. In the invention, the vinyl acetate or the isopropenyl acetate is adopted to directly carry out the acetylation reaction with 5-deoxidization-D-ribose in the aqueous solution, and the 1,2,3-tri-O-acetyl-5-deoxidization-D-ribose with higher beta isomer purity is finally obtained.

Description

Technical field [0001] The invention relates to a preparation method of pharmaceutical intermediates, specifically to a preparation method of 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose. Background technique [0002] Capecitabine (trade name Xeloda) is a nucleoside anticancer drug mainly used to treat breast cancer and rectal cancer. US patent document US5453497A discloses a method of condensing 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose and 5-fluorocytosine, then acylating, and finally hydrolyzing to obtain The capecitabine method. [0003] There are several main methods for preparing 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose: [0004] Chinese patent document CN101012252 (Application No.: 200710019873.7) discloses a method that uses inosine as raw material, first performs iodine reaction with iodine, then performs liquid phase hydrogenation with hydrogen, then performs acetylation reaction with acetic anhydride, and finally breaks the bond. Deglycoside yields 1,2,3-tri-O-acetyl-5-deoxy...

AI Technical Summary

Problems solved by technology

The disadvantage of this method is: the cost of iodine / imidazole / triphenylphosphine system is high, and the acetylation temperature is high, there are many by-products, and it is difficult to crystallize

The disadvantage of this step is: (1) This step uses a large amount of pyridine or triethylamine, which is extremely harmful to the environment

(2) Since it takes a lot of time and energy to remove water in the reaction system when using acetic anhydride

[0007] The ratio of β:α isomers in the 1,2,3-tri-O-acetyl-5-deoxy-D-ribose finally obtained according to the method of US patent document US4340729A and Chinese patent document 200710191269.2 is 3:1~9 : 1, less than 70% of effective β-isomers, so the purity is lower, and the yield of β-isomers is less than 55%

Therefore, before carrying out the acetylation reaction, these documents must be dried first, and often only the method of carrying water with a solvent can be used for drying, which requires a large amount of solvent consumption, and the operation time is also very long. It also consumes a lot of energy

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