• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Comprising reacting compound (IV) with compound (V) in a solvent to give (S)-mitiglinide (II) and compound (III) as a by- product; removing the solvent and adding ethyl acetate to precipitate compound (III); collecting the solid and applying at least one cycle process comprising: - refluxing the solution of compound (III) with an organic solvent to give (S)-mitiglinide (II) and further compound (III) as a by-product, - removing the organic solvent and adding ethyl acetate to precipitate compound (III); and - separating the mother liquors from the solid, and mixing all the mother liquors; removing the ethyl acetate from the mother liquors to obtain (S)-mitiglinide.
    公开号:ES2546362A2
    申请号:ES201490131
    申请日:2013-06-13
    公开日:2015-09-22
    发明作者:Juan Huguet Clotet；Isabel Navarro Muñoz
    申请人:Laboratorios Lesvi SL；
    IPC主号:
    专利说明:

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    mother contains the desired product represented by the formula (II). (S) -mitiglinide can be isolated by a known industrial process such as evaporation, distillation, concentration, filtration, centrifugation or phase separation.
    5 This process cycle can be repeated as many times as desired so that in each new cycle one obtains (S) -mitiglinide and more by-product.
    Advantageously, the invention provides a process with a higher atomic efficiency, due to the fact that the ratio of atoms of the respective initial reagents to be
    10 incorporated into the final product is as high as possible. The increase in atomic efficiency also leads to a reduction in the amount of waste generated in the reaction process, which will have to be treated.
    Therefore, the compound of formula (II) obtained according to the process herein
    The invention that can be used to obtain mitiglinide calcium salt (I), a pharmaceutically acceptable salt, or a hydrate thereof is also within the scope of the present invention. DETAILED DESCRIPTION OF THE INVENTION
    In order to provide an effective process for obtaining (S) -mitiglinide, the inventors have reproduced the reaction between (S) -3-benzyl dihydrofuran-2,5-dione of formula
    (IV) and (3aR, 7aS) octahydro-1H-isoindole of formula (V) described in the "Synthesis of KAD-1229 through amidation of bis-activated esters and discussion of regioselectivity
    25 of the reactions ", Acta Chimica Sinica, Vol 67, 2009, No. 22, 2635-2640, to know if other by-products other than acid (3S) -3-benzyl-4- (2-hexahydro-1Hisoindole ( 3H) -yl) -4-oxobutanoic of formula (III).
    Advantageously, it has been found that although the energy efficiency in the reaction
    The aforementioned reproduced is very poor, about 50 percent, no additional by-products other than the compound of formula (III) are generated.
    In view of the prior art, the problem to be solved by the present invention can be seen as providing a method of obtaining (S) -mitiglinide with a higher atomic efficiency and a lower amount of waste to be treated, which is also industrially acceptable. , safe for the environment and in which (S) -mitiglinide is obtained with high
    9
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    权利要求:
    Claims (1)
    [1]
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    同族专利:
    公开号 | 公开日
    ES2546362R1|2015-09-30|
    ES2546362B1|2016-07-07|
    WO2013189829A1|2013-12-27|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    AU654331B2|1991-03-30|1994-11-03|Kissei Pharmaceutical Co. Ltd.|Succinic acid compounds|
    FR2765578B1|1997-07-03|1999-09-10|Adir|PROCESS FOR THE PREPARATION OF A SUBSTITUTED PERHYDROISOINDOLE|CN105330585B|2015-11-05|2018-03-06|常州大学|A kind of preparation method of Mitiglinide Calcium|
    法律状态:
    2016-07-07| FG2A| Definitive protection|Ref document number: 2546362 Country of ref document: ES Kind code of ref document: B1 Effective date: 20160707 |
    优先权:
    申请号 | 申请日 | 专利标题
    EP12173115|2012-06-22|
    EP12173115|2012-06-22|
    PCT/EP2013/062272|WO2013189829A1|2012-06-22|2013-06-13|Process for obtaining -2-benzyl-4--hexahydro-1 h-isoindol- 2-yl)-4-oxobutanoic acid and salts thereof|
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