A kind of synthetic method of capecitabine

A kind of synthetic method of capecitabine

  • CN 104,744,537 B
  • Filed: 04/09/2015
  • Issued: 06/08/2018
  • Est. Priority Date: 04/09/2015
  • Status: Active Grant
First Claim
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1. a kind of synthetic method of capecitabine, which is characterized in that the synthetic method specifically comprises the following steps:

  • Under ice bath,Controlled at 1 DEG C, 23.1mmol n-amyl chlorocarbonates are slowly dropped into 22.6mmol K2CO3, 2.65mmol dimethylamino pyrrolesIn the 30mL toluene solutions of bis--O- acetyl group -5'"'"'- deoxidation -5- fluorine cytidines of pyridine and 14.5mmol 2'"'"', 3'"'"'-, insulation reaction45min;

    Filtering, filtrate are washed successively with the hydrochloric acid, 10mL water and 10mL saturated common salts of the 0.2M of 10mL, and anhydrous sodium sulfate is doneIt is dry, solvent is removed under reduced pressure and obtains white solid 5.7g, yield 84.7%;

    Previous step reaction product is added in into 100mL there-necked flasksPenta bis--O- acetyl group -5'"'"'- deoxidation -5- fluorine cytidine 5g, 40mL methanol of oxygen carbonyl -2'"'"', 3'"'"'- of N-;

    It is cooled to after 0 DEG C and is added dropwise 2M'"'"'sThe 15 beta-hydroxy jervine 2mL of potassium hydroxide 10mL and 2M, maintain 5 to 15 DEG C of temperature, and 2M hydrochloric acid tune pH is added dropwise after 1 hour in reactionIt is worth to 6;

    Merge organic phase after being extracted in three times with 150mL dichloromethane, respectively with 100mL saturated sodium bicarbonate aqueous solutions,100mL water washings;

    Organic phase concentrates after being dried with anhydrous sodium sulfate, and capecitabine white powder is obtained with 16mL re-crystallizing in ethyl acetateLast 3.9g, yield 96.1%.

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