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Separation and purification method for (S)-1-amino-3-chloro-2-propanol hydrochloride

A technology of propanol hydrochloride, -1-n-boc-, which is applied in the field of chiral drug intermediates, can solve problems such as the difficulty of debenzylation of hydrochloric acid, achieve the elimination of separation and purification process, improve quality, chemical purity and optical The effect of high purity

Inactive Publication Date: 2013-12-25
重庆惠健生物科技有限公司
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  • Application Information

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Problems solved by technology

But this route is actually very difficult to use hydrochloric acid debenzylation

Method used

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  • Separation and purification method for (S)-1-amino-3-chloro-2-propanol hydrochloride
  • Separation and purification method for (S)-1-amino-3-chloro-2-propanol hydrochloride
  • Separation and purification method for (S)-1-amino-3-chloro-2-propanol hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0026] (1) Synthesis of (S)-1-amino-3-chloro-2-propanol hydrochloride: 270g (5.58mol) 95% ethanol, 106g (1.0mol) benzaldehyde, 100g ( 1.65mol) 28% ammonia water, stirred at 20°C for 1h; added 92.5g (1.0mol) (S)-epichlorohydrin, heated to 40°C for 7h, cooled to 25°C, and kept for 14h to obtain (S)-1 - benzylamino-3-chloro-2-propanol reaction solution; (S)-1-benzylamino-3-chloro-2-propanol reaction solution was added with 300ml of toluene and 300ml of 31% hydrochloric acid, hydrolyzed at 40°C 4h, liquid separation, the water phase was extracted twice with toluene (2×100ml), and the benzaldehyde was separated to obtain (S)-1-amino-3-chloro-2-propanol hydrochloride reaction solution;

[0027] (2) Preparation of (S)-1-N-Boc-amino-3-chloro-2-propanol: (S)-1-amino-3-chloro-2-propanol hydrochloride obtained in step (1) The pH of the salt reaction solution was adjusted to 8 with sodium carbonate, 208 g (1.0 mol) of Boc anhydride was added in batches, and the reaction was carried out a...

Embodiment 2

[0030](1) Synthesis of (S)-1-amino-3-chloro-2-propanol hydrochloride: 340g (7mol) 95% ethanol, 106g (1.0mol) benzaldehyde, 110g (1.8 mol) 28% ammonia water, stirred at 30°C for 1h; added 92.5g (1.0mol) (S)-epichlorohydrin, heated to 50°C for 8h, cooled to 20°C, and kept for 18h to obtain (S)-1- Benzylamino-3-chloro-2-propanol reaction liquid; add 500ml of toluene and 350ml of 31% hydrochloric acid to (S)-1-benzylamino-3-chloro-2-propanol reaction liquid, hydrolyze at 30℃ for 5h , liquid separation, the water phase was extracted twice with toluene (2×100ml), and the benzaldehyde was separated to obtain (S)-1-amino-3-chloro-2-propanol hydrochloride reaction liquid;

[0031] (2) Preparation of (S)-1-N-Boc-amino-3-chloro-2-propanol: (S)-1-amino-3-chloro-2-propanol hydrochloride obtained in step (1) The pH of the salt reaction liquid was adjusted to 9 with sodium carbonate, 250 g (1.2 mol) of Boc anhydride was added in batches, and the reaction was carried out at 20°C for 5 h, and...

Embodiment 3

[0034] (1) Synthesis of (S)-1-amino-3-chloro-2-propanol hydrochloride: 484g (10mol) 95% ethanol, 106g (1.0mol) benzaldehyde, 120g (2.0 mol) 28% ammonia water, stirred at 20°C for 2h; added 92.5g (1.0mol) (S)-epichlorohydrin, heated up to 40°C for 10h, cooled to 30°C, and kept for 10h to obtain (S)-1- Benzylamino-3-chloro-2-propanol reaction liquid; add 400ml of toluene and 400ml of 8mol / l hydrochloric acid to (S)-1-benzylamino-3-chloro-2-propanol reaction liquid, hydrolyze at 50℃ 3h, liquid separation, the water phase was extracted twice with toluene (2×100ml), and the benzaldehyde was separated to obtain (S)-1-amino-3-chloro-2-propanol hydrochloride reaction solution;

[0035] (2) Preparation of (S)-1-N-Boc-amino-3-chloro-2-propanol: (S)-1-amino-3-chloro-2-propanol hydrochloride obtained in step (1) The pH of the salt reaction solution was adjusted to 10 with sodium carbonate, 327 g (1.5 mol) of Boc anhydride was added in batches, and the reaction was carried out at 40°C for...

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Abstract

The invention discloses a separation and purification method for (S)-1-amino-3-chloro-2-propanol hydrochloride. The separation and purification method comprises the steps: with (S)-epoxy chloropropane as a chiral source and ethanol as a solvent, carrying out condensation with benzaldehyde and ammonia to obtain (S)-1-benzylideneamino-3-chloro-2-propanol, then carrying out acidolysis of the obtained (S)-1-benzylideneamino-3-chloro-2-propanol to obtain (S)-1-amino-3-chloro-2-propanol hydrochloride and benzaldehyde; after separating and removing benzaldehyde, employing di-tert-butyl dicarbonate ester for protection, employing an organic solvent for extraction, and carrying out deprotection to achieve effective separation and purification. The separation and purification method disclosed by the invention abolishes a tedious separation and purification process, effectively removes by-products and inorganic salts in the product, significantly increases the quality of (S)-1-amino-3-chloro-2-propanol hydrochloride, has the characteristics of high product yield, high chemical purity and high optical purity, is also simple in process, and is suitable for large-scale production of (S)-1-amino-3-chloro-2-propanol hydrochloride.

Description

technical field [0001] The invention belongs to the technical field of chiral drug intermediates, in particular to a separation and purification method of (S)-1-amino-3-chloro-2-propanol hydrochloride. Background technique [0002] Linezolid (Formula I) is the world's first oxazolidinone antibacterial drug developed by Pfizer, and its trade name is Zyvox. Clinically, it is mainly used to treat infections caused by Gram-positive cocci, including suspected or confirmed nosocomial-acquired pneumonia (HAP), community-acquired pneumonia (CAP), complicated skin or skin and soft tissue infection (SSTI) caused by MRSA, and Vancomycin-resistant Enterococcus (VRE) infection. Linezolid was approved by the FDA for marketing in the United States in 2000, and was approved by the SFDA for marketing in China in 2007. At present, linezolid has been widely used in more than 40 countries around the world. Linezolid is currently the best-selling antibacterial drug with a global market sales o...

Claims

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Application Information

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IPC IPC(8): C07C215/08C07C213/02C07C213/10
Inventor 夏仕文方国兰何从林徐红梅
Owner 重庆惠健生物科技有限公司
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