Method for preparing gabapentin with chemo-enzymatic method

Method for preparing gabapentin with chemo-enzymatic method

  • CN 104,911,225 A
  • Filed: 06/05/2015
  • Published: 09/16/2015
  • Est. Priority Date: 06/05/2015
  • Status: Active Application
First Claim
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1. the method for a chemo-enzymatic process production gabapentin, it is characterized in that described method is:

  • (1) enzyme catalysis;

    with the immobilized cell containing nitrilase for enzyme source, with 1-cyanocyclohexanoic base acetonitrile for substrate, with pure water or phosphate buffered saline buffer for reaction medium, 20-50 DEG C, carry out conversion reaction, after reaction terminates under 100-350rpm condition, conversion reaction liquid is filtered, obtain filter cake and filtrate, filter cake reclaims enzyme source, and filtrate is the conversion fluid containing 1-cyanocyclohexanoic guanidine-acetic acid;

    The described immobilized cell containing nitrilase is prepared as follows;

    added in damping fluid or distilled water through the wet thallus that fermentation culture obtains by the recombination engineering bacteria containing nitrilase gene, make bacteria suspension;

    In bacteria suspension, add carrier, stirring and evenly mixing, then add polymine, stir flocculation 0.5 ~ 2h, then add glutaraldehyde and be cross-linked, after 10 ~ 25 DEG C of crosslinked 0.5 ~ 2h of stirring, abandoning supernatant, after vacuum filtration, obtains immobilized cell;

    Described carrier is diatomite, perlite or gac;

    In described carrier and bacteria suspension, wet thallus weight ratio is 0.01 ~ 0.1;


    (2) hydrogenation reaction;

    get the conversion fluid of step (1) containing 1-cyanocyclohexanoic guanidine-acetic acid in hydrogenation reaction kettle, add hydrogenation catalyst, pass into hydrogen, in 0-300 DEG C, stirring reaction under 400-1200rpm condition, after reacting completely, reaction solution is cooled to 30-80 DEG C, emptying hydrogen, by reacting liquid filtering, obtain filtrate and filter cake, filter cake reclaims catalyzer, filtrate adds isopyknic dichloromethane extraction after being cooled to room temperature, stratification, obtain organic phase and aqueous phase, organic phase steams to obtain lactamase gabapentin crystal through revolving, lactamase gabapentin crystal is hydrolyzed to react and generates Gabapentin hydrochloride, then Gabapentin hydrochloride carries out quaternization, obtain gabapentin, methylene dichloride recycling, aqueous phase reclaims ammonia and waste water by ammonia still process method, and waste water then reclaims as reaction medium for the enzymic catalytic reaction in step (1), described hydrogenation catalyst is Raney'"'"'s nickel.

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