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Preparation method of biotin intermediate impurity

An intermediate, biotin technology, applied in the direction of magnesium organic compounds, organic chemistry, etc., can solve the problems such as the inability to obtain high-purity transition state hydroxyl compounds, and achieve the effect of simple and easy preparation method and quality control.

Active Publication Date: 2016-03-23
BENGBU BBCA MEDICINE SCI DEV
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Problems solved by technology

[0003] According to the literature retrieved at present, the stable synthetic method of the high-purity product has not yet been found. The method reported in the literature uses sulfuric acid to carry out hydrolysis, which is prone to dehydration and mainly generates the compound shown in the following formula (VI), but cannot obtain high-purity transition state Hydroxide

Method used

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  • Preparation method of biotin intermediate impurity
  • Preparation method of biotin intermediate impurity
  • Preparation method of biotin intermediate impurity

Examples

Experimental program
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Effect test

Embodiment 1

[0048] Biotin intermediate impurity 5-((3aS,4S,6aR)-1,3-dibenzyl-4-hydroxy-2-oxo-1H-thiophene[3,4-d]imidazole-4-yl)pentyl The preparation method of acid, comprises the following steps:

[0049] a) Grignard reaction

[0050] Under the protection of nitrogen, add 5.8g of magnesium chips and 60ml of anhydrous tetrahydrofuran to the reaction flask, heat and reflux for 30min, add 1 iodine particle (0.3g) to the reaction flask, and dropwise add 25g of 1,4-dihydrofuran to the reaction flask Butyl bromide and 125ml tetrahydrofuran were added dropwise and continued to reflux for 3h; a reaction solution containing a Grignard reagent as shown in structural formula (I) was obtained.

[0051] b) Addition reaction

[0052] Add 21.8g of thiolactone ((3aS,6aR)-1,3-dibenzyltetrahydro-1H-thiophene[3,4-d]imidazole-2,4-dione to the reaction flask, then add 200ml of tetrahydrofuran Dissolved, transferred to the dropping funnel, added dropwise to the reaction solution prepared in step a) under n...

Embodiment 2

[0057] Biotin intermediate impurity 5-((3aS,4S,6aR)-1,3-dibenzyl-4-hydroxy-2-oxo-1H-thiophene[3,4-d]imidazole-4-yl)pentyl The preparation method of acid, its difference with embodiment 1 is only in step C) CO 2 The feeding temperature of the mixture is -20°C, the ventilation time is 4h, and the addition amount of other materials, reaction conditions and post-treatment process are consistent with Example 1. Finally, 42.5 g of the light yellow oily liquid of the final product was obtained. The yield was 83%.

[0058] According to the same method as in Example 1, the content of the obtained final product was 98.7% through HPLC detection.

[0059]It can be seen from the above examples that the process of the present invention is especially suitable for synthesis under laboratory conditions, without harsh reaction conditions, and the resulting product has high purity, which can be used for the detection of impurities in the corresponding intermediates of biotin.

experiment example 1

[0061] The mass spectrogram of the final product that embodiment 1 makes is shown in figure 1 .

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Abstract

The invention provides a preparation method of a biotin intermediate impurity with the structural formal shown in a formula (V). Thiolactone and the Grignard reagent are taken as raw materials, and the high-purity intermediate impurity is obtained through addition and hydrolysis. The preparation method is simple and easy and is particularly suitable for preparation in a laboratory.

Description

technical field [0001] The present invention relates to the synthetic technology of compound, specifically, relate to the preparation method of biotin intermediate impurity. Background technique [0002] Biotin, also known as vitamin H and coenzyme R, is a water-soluble vitamin and also belongs to the vitamin B family, B7. It is a necessary substance for the synthesis of vitamin C and is indispensable for the normal metabolism of fat and protein. It is a necessary nutrient to maintain the natural growth, development and normal human body function and health of the human body. The synthesis of biotin is through the reaction of intermediate thiolactone through double formatting, hydrogenation, debenzylation, and cyclization to synthesize biotin. Double formatting is an important reaction step. If the hydrolysis reaction is not complete, unolefinized impurities may be introduced. adversely affect subsequent reactions. In order to effectively control the impurity that may be ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04C07F3/02
CPCC07D495/04C07F3/02
Inventor 郑爱韦亚锋李士桥林文龙胡媛
Owner BENGBU BBCA MEDICINE SCI DEV
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