Preparation method of L-2-aminobutanamide hydrochloride

A technology of aminobutyramide and DL-2-, applied in the preparation of carboxylic acid amide optical isomers, organic chemistry, etc., can solve the problems of product suction filtration and unstable quality, the impact of splitting process, production restrictions, etc., to achieve The effect of low equipment requirements, simple and safe unit operation, and stable quality

Active Publication Date: 2012-07-18
ABA CHEM NANTONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in actual production, it was found that the crude product of DL-2-aminobutyramide contained many unknown impurities, which had a great impact on the subsequent separation process, resulting in product suction filtration and unstable quality, and production was subject to certain restrictions

Method used

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  • Preparation method of L-2-aminobutanamide hydrochloride
  • Preparation method of L-2-aminobutanamide hydrochloride
  • Preparation method of L-2-aminobutanamide hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1.1 Purification:

[0040] In a 1000ml flask, dissolve 100g of crude DL-2-aminobutyramide in 500ml of water, add 106g of benzaldehyde, the solid slowly precipitates, continue to stir at room temperature for 5 hours, filter, wash with a small amount of water, and dry the solid under vacuum at 30°C. 158 g of vortexed Schiff base was obtained with a yield of 85.0%.

[0041] As a preferred version of the purification step, the aromatic aldehyde can also be salicylaldehyde, p-tolualdehyde, p-ethylbenzaldehyde, 3,4-dimethylbenzaldehyde and 2,4,6-trimethylbenzaldehyde One or several, wherein, the mol ratio of DL-2-aminobutyramide crude product to aromatic aldehyde can be 1: 0.8~2, preferably 1:1~1.5; Mixed DL-2-aminobutanamide crude product and The weight ratio of water may be 1:1-100, preferably 1:5-20.

[0042] 1.2 Split:

[0043] In a 1000ml flask, add 150g of Schiff's base and 500ml of absolute ethanol, stir to dissolve the solid, add 30g of L-tartaric acid / 150ml of abs...

Embodiment 2

[0052] 2.1 Purification:

[0053] In a 1000ml flask, dissolve 100g of DL-2-aminobutanamide crude product in 650ml of water, add 106g of benzaldehyde, the solid slowly precipitates out, continue to stir at room temperature for 5 hours, filter, wash with a small amount of water, and dry the solid under vacuum at 30°C to obtain 162 g of vortexed Schiff base, yield 87.1%.

[0054] 2.2 Split:

[0055] In a 1000ml flask, add 150g of Schiff's base and 500ml of anhydrous methanol, stir to dissolve the solid, add 30g of L-tartaric acid / 150ml of anhydrous methanol solution at 20-25°C, react at 20-25°C for 6 hours, filter, and use A small amount of anhydrous methanol was washed, and the solid was vacuum-dried at 60° C. to constant weight to obtain 58.8 g of L-2-aminobutyramide tartrate as a solid, with a yield of 41.5%.

[0056] 2.3 Free into salt:

[0057] In a 500ml flask, add 50g of L-2-aminobutyramide tartrate, 250ml of absolute ethanol, cool to 0-5°C, inject ammonia gas to satura...

Embodiment 3

[0061] 3.1 Purification:

[0062] In a 1000ml flask, dissolve 100g of DL-2-aminobutanamide crude product in 650ml of water, add 122g of benzaldehyde, the solid slowly precipitates out, continue to stir at room temperature for 5 hours, filter, wash with a small amount of water, and dry the solid under vacuum at 30°C to obtain 187 g of vortexed Schiff base, yield 93.0%.

[0063] 3.2 Split:

[0064] In a 1000ml flask, add 180g of Schiff's base and 500ml of absolute ethanol, stir to dissolve the solid, add 33g of L-tartaric acid / 150ml of absolute ethanol solution at 20-25°C, react at 20-25°C for 6 hours, filter, and use After washing with a small amount of absolute ethanol, the solid was vacuum-dried at 70° C. to constant weight to obtain 70.0 g of L-2-aminobutyramide tartrate solid, with a yield of 45.0%.

[0065] 3.3 Free salt formation:

[0066] In a 500ml flask, add 60g of L-2-aminobutyramide tartrate, 300ml of absolute ethanol, cool to 0-5°C, feed ammonia to saturation, co...

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Abstract

The invention provides a preparation method of L-2-aminobutanamide hydrochloride. The method comprises the following steps: based on crude DL-2-aminobutanamide as a starting raw material, reacting with aromatic aldehyde to form DL-Schiff-base, separating, dissociating, and salifying to obtain L-2-aminobutanamide hydrochloride, wherein the Schiff base can be directly separated by using L-tartaric acid, the chiral purity ee value of the product is no less than 99%, the quality is stable, and the separation mother liquor can be recycled through racemization. According to the invention, the raw materials used in each step of the method are cheap and available, the unit operations are simple and safe, the post-treatment is convenient, the requirements on the equipment are low and the method issuitable for industrialized production.

Description

technical field [0001] The invention relates to the preparation of pharmaceutical intermediates, in particular to a preparation method of L-2-aminobutyramide hydrochloride, a chiral drug levetiracetam intermediate. Background technique [0002] Levetiracetam (Levetiracetam) is a new antiepileptic drug that can reduce partial seizures as adjuvant therapy or monotherapy. In 1999, it was approved by the US FDA for the adjuvant treatment of partial epileptic seizures in adults. In 2005, its oral tablets and solutions were approved for the adjuvant treatment of first seizures in children and adolescents aged 4 and above. It was approved for listing in my country in March 2007. This product has a unique mechanism of action different from other antiepileptic drugs. It is the only antiepileptic drug that has been confirmed to bind to the synaptic vesicle protein SV2A in the presynaptic nerve endings. Its combination with SV2A can inhibit abnormalities in the epilepsy circuit. disc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C237/06C07C231/20
Inventor 江岳恒阙利民蔡彤
Owner ABA CHEM NANTONG
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