A method for preparing (s)-2-aminobutanamide by enzymatic method

A technology for the preparation of aminobutyramide and enzymatic method, which is applied in the field of preparation of the key intermediate - 2-aminobutanamide, can solve the problems of low yield, large environmental hazards, and high cost of the preparation method, and achieve low process cost and increase production. efficiency and cost reduction

Inactive Publication Date: 2011-11-30
SYNCOZYMES SHANGHAI
View PDF10 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The cost of the current preparation method is high, the yield is low, the environmental hazards are large, and the process conditions are not suitable for industrial scale-up. Therefore, a high-ef

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A method for preparing (s)-2-aminobutanamide by enzymatic method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 12

[0013] The synthesis of embodiment 12-aminobutyronitrile 2

[0014] In a 100 ml three-necked flask, add 8.45 grams of potassium cyanide (1.3 equivalents), 40 milliliters of 25% ammonia water, and then add 7.87 grams of ammonium chloride (1.5 moles), and dissolve under stirring. 5.8 g (0.1 mole) of n-propanal (compound 1) was added dropwise, the temperature was controlled at 10-25° C., stirred overnight, and extracted three times with dichloromethane. The organic extracts were combined, washed with 20 ml of saturated brine, and dried by adding 10 g of anhydrous magnesium sulfate. After filtration, dichloromethane was removed by rotary evaporation in a water bath at 30°C under reduced pressure to obtain about 6.7 g of 2-aminobutyronitrile as light yellow oily liquid with a yield of 79.8%.

Embodiment 2

[0015] The screening of embodiment 2 nitrile hydratases

[0016] The 2-aminobutyronitrile obtained in Example 1 is formulated into a solution of 10 grams per liter, and 24 kinds of nitrile hydratases of 5 mg NHT-101~NHT-124 are added respectively in parallel reaction vessels, and 0.45 milliliters of phosphate buffer saline is added (Na 2 HPO 4 / NaH 2 PO 4 , 0.1M, pH 7.2), and then add 0.05 ml of α-aminobutyronitrile solution, shake overnight at room temperature, and detect the reaction by LC-MS. As a result, 13 enzymes can react to produce products. These 13 enzymes are carried out selective comparison, control reaction time, make its reaction conversion rate 80% (CR (+) column; UV 200nm detection; mobile phase: perchloric acid aqueous solution (pH 1.2)), the three enzymes were used to prepare (S)-2-aminobutyramide.

Embodiment 3

[0017] The preparation of embodiment 3 (S)-2-aminobutanamide (ES-NHT-105)

[0018] Add 50 mg of 2-aminobutyronitrile, 1 mg of nitrile hydratase NHT-105, and 5 ml of phosphate buffer (Na 2 HPO 4 / NaH 2 PO 4 , 0.1M, pH 7.2), after reacting on a rotary shaker at 160 rpm at 30°C for 15 hours, samples were taken for HPLC analysis, the conversion rate was 33%, and the ee value was 82%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a synthesis process for preparing (S)-2-aminobutyramide by enzymatic method. The current preparation method has problems such as high cost, low yield, and large environmental hazards. The technical scheme adopted in the invention is: using 2-aminobutyronitrile as a starting material to prepare (S)-2-aminobutyramide in one step in a buffer solution system through enzyme catalysis. In the present invention, water is used as a solvent in the main process, without using a large amount of organic solvents harmful to the environment, the whole process cost is low, and it is beneficial to large-scale industrial preparation.

Description

technical field [0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to a method for preparing a key intermediate (S)-2-aminobutyramide for the synthesis of levetiracetam. technical background [0002] Levetiracetam is a new type of antiepileptic drug. It is a second-generation acetylcholine agonist related to piracetam in structure developed by UCB Company in Belgium. It is mainly used for the treatment of localized and secondary generalized epilepsy. Its chemical name is: (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide, and its structural formula is as follows: [0003] [0004] In the current levetiracetam synthesis process, most of them prepare levetiracetam through (S)-2-aminobutyric acid or (S)-2-aminobutyramide two intermediates, especially through (S)- The preparation of levetiracetam by 2-aminobutyramide is the main process of industrial production at present. The levetiracetam prepared by this process is low in cost and...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C12P13/02
Inventor 祝俊陶军华苏金环孙勇黄悦金志平谢作念陈见阳
Owner SYNCOZYMES SHANGHAI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap