Novel process for the recovery of beta acetylfuranoside

Abstract

There is provided an improved method for the recovery of residual, unseparated β-ACF from reaction mixtures remaining from an initial synthesis of ACF, which is in particular usable on a large industrial scale, more particularly in the production of capecitabine.

1 . A method for recovery of initially not separated β-ACF from mother liquor remaining from the synthesis of ACF, wherein the β-ACF is recovered by a combination of at least one distillation method and at least one chemical reaction step. 
     
     
         2 . The method according to  claim 1  comprising the following sequential steps:
 a) Evaporation to less than 1% residual solvent of the mother liquor remaining from an initial synthesis of ACF, to increase the content of residual α/β-ACF from about 8 to 15 weight-% to about 25 to 45 weight-%, followed by distillation to about 60 to 80 weight-% and subsequent crystallization of β-ACF out of the distillate by adding a suitable solvent;   b) Chemical conversion of α/β-ACF mixture remaining in the mother liquor of step a), to β-ACF by de-acetylation and subsequent re-acetylation, followed by crystallization of β-ACF by addition of a suitable solvent;   c) Optional repetition of step a) and b) in a sequential (clockwise) cyclic process.   
     
     
         3 . The process according to  claim 2 , wherein the distillation to about 60 to 80 weight-% of step a) is carried out at 1 to 3 mbar and 200 to 210° C. heating temperature in a continuous thin-film evaporator. 
     
     
         4 . The process according to  claim 2  or  3 , wherein step b) comprises the de-acetylation of α/β-ACF in the presence of a suitable base, followed by neutralization with a suitable acid and further followed by the re-acetylation reaction in the presence of suitable base, a suitable catalyst and a suitable acetylating agent. 
     
     
         5 . The process according to any one of  claims 1  to  4  for use during the manufacture of capecitabine. 
     
     
         6 . The novel processes and uses substantially as described herein.