A kind of method for preparing d-biotin thiolactone intermediate

Abstract

The invention discloses a method for preparing a D-biotin thiolactone intermediate, which comprises the following steps: a) adding the lactone intermediate and potassium thioacetate to a reaction vessel at a mass ratio of 2:1 to 2.4:1 , heating until the reaction system is in a completely molten state, and then insulated and stirred for 1 to 5 hours; b) cooling down to 50 to 80°C, and then adding 2 to 10 milliliters of water to the reaction system according to 1 gram of lactone intermediate; c) ) lowering the temperature of the reaction system to 0-10°C while stirring, and then maintaining the temperature and continuing to stir for 1-5 hours; d) filtering, and the collected solid is the D-biotinthiolactone intermediate. The invention realizes the participation of no solvent in the reaction, not only has no problems of solvent environmental protection and recovery, but also has low preparation cost and very simple operation process, especially, the high-purity target object with HPLC purity ≥ 99.5% can be obtained only by filtering and washing with water , and the mass yield ≥ 95%.

Description

technical field [0001] The invention relates to a method for preparing a D-biotin thiolactone intermediate, belonging to the technical field of medicinal chemistry. Background technique [0002] D-Biotin, also known as vitamin H, is one of the water-soluble B vitamins. It is widely distributed in animal and plant tissues, such as mainly in liver, kidney, egg yolk, yeast and milk, and also in Plant seeds, pollen, molasses, fungi, fresh vegetables and fruits. D-biotin is an important vitamin, the prosthetic group of carboxylase, and one of the important coenzymes in the intermediate metabolism of sugar, protein and fat. The lack of biotin in humans can cause symptoms such as dermatitis, loss of appetite, nausea, vomiting, depigmentation, and hair loss. D-biotin is also necessary for the normal growth of poultry and livestock, so it is widely used in medical treatment and feed additives. [0003] The chemical name of D-biotin is: (3aS-(3aα,4β,6aα)-hexahydro-2-oxo-1H-thieno[3...

AI Technical Summary

Problems solved by technology

[0007] Because the reaction solvent in the above-mentioned method is DMA, its boiling point is as high as 163 ℃, if reclaiming DMA by the mode of underpressure distillation, following problem can be produced: if carry out underpressure distillation under the lower situation of keeping temperature, then the efficiency of reclaiming DMA is not enough High; if you want to improve the recovery rate of DMA, you must increase the distillation temperature, especially the distillation temperature in the later stage, but such consequences will cause a large amount of impurities to be produced and reduce the purity of the product; if it is removed by washing, a large amount of DMA-containing Wastewater, environmental protection problems are not easy to solve

In addition, this method needs to add a large amount of water and toluene to process the reaction product after the reaction is completed, so as to extract the product into the toluene layer. The problems that arise in this way are: first, the environmental protection problems of a large amount of stratified waste water will be generated, and second, a large amount of toluene is required Solvents lead to high production costs. Third, the operation is cumbersome and the preparation period is long.

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