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Synthesis method of (R)-(-)-1-methyl-3-amphetamine

A synthetic method and technology of amphetamine, which is applied in the field of synthesis of the key intermediate - 1-methyl-3-amphetamine, can solve the problems of high cost, unsuitability for industrial production, harsh synthesis conditions, etc.

Inactive Publication Date: 2016-01-13
湖南华腾制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It mainly solves the problem that the synthesis conditions of (R)-(-)-1-methyl-3-amphetamine compound are harsh, the cost is high, and it is not suitable for industrial production

Method used

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  • Synthesis method of (R)-(-)-1-methyl-3-amphetamine
  • Synthesis method of (R)-(-)-1-methyl-3-amphetamine
  • Synthesis method of (R)-(-)-1-methyl-3-amphetamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Synthesis of compound II:

[0021]

[0022] Add phenylpropionaldehyde (55g, 0.41mol) to tetrahydrofuran (400ml), then add tritylamine (106.2g, 0.41mol) and tetrabutyl titanate (278.8g, 0.82mol), and stir at room temperature for 1 hour , and then refluxed for 4 hours, TLC spot plate detected that the reaction of the raw materials was complete, cooled to room temperature, added saturated sodium bicarbonate, stirred, stood still, separated into layers, separated the organic phase, concentrated under reduced pressure, and added saturated saline and ethyl acetate to the residue Esters, extraction, standing to separate layers, separating the organic phase, drying with anhydrous sodium sulfate, filtering to remove the desiccant, concentrating under reduced pressure to obtain the crude product of compound II, using ethyl acetate:petroleum ether=3:7 (volume ratio ) recrystallization to obtain off-white solid compound II99g, yield 71%.

[0023] 1HNMR (400MHz, CDCl 3 ): δppm7...

Embodiment 2

[0029] Synthesis of compound II:

[0030]

[0031] Add phenylpropionaldehyde (55g, 0.41mol) to toluene (400ml), then add tritylamine (106.2g, 0.41mol) and tetrabutyl titanate (278.8g, 0.82mol), and stir at room temperature for 1 hour , and then refluxed for 4 hours, TLC spot plate detected that the reaction of the raw materials was complete, cooled to room temperature, added saturated sodium bicarbonate, stirred, stood still, separated into layers, separated the organic phase, concentrated under reduced pressure, and added saturated saline and ethyl acetate to the residue Esters, extraction, standing to separate layers, separating the organic phase, drying with anhydrous sodium sulfate, filtering to remove the desiccant, concentrating under reduced pressure to obtain the crude product of compound II, using ethyl acetate:petroleum ether=3:7 (volume ratio ) recrystallized to obtain 103.1 g of off-white solid compound II, with a yield of 74%.

[0032] 1HNMR (400MHz, CDCl 3 )...

Embodiment 3

[0038] Synthesis of compound II:

[0039]

[0040] Add phenylpropionaldehyde (55g, 0.41mol) to 1,4-dioxane (450ml), then add tritylamine (106.2g, 0.41mol) and tetraethyl titanate (187g, 0.82mol) , stirred at room temperature for 1 hour, and then refluxed for 4 hours. The reaction of the raw materials was detected by TLC spotting. Saturated saline and ethyl acetate, extraction, standing to separate layers, separating the organic phase, drying with anhydrous sodium sulfate, filtering to remove the desiccant, concentrating under reduced pressure to obtain the crude product of compound II, using ethyl acetate:petroleum ether= 3:7 (volume ratio) recrystallization to obtain off-white solid compound II96g, yield 68.9%.

[0041] 1HNMR (400MHz, CDCl 3 ): δppm7.49~7.31(m,5H), 7.07~6.92(m,15H), 6.84(m,1H), 2.63(t,2H), 1.8(t,2H); m / z=376(M +H)+.

[0042] Synthesis of (R)-(-)-1-methyl-3-amphetamine:

[0043]

[0044] Compound II (37.5g, 0.1mol) was added to diethyl ether (500ml), ...

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Abstract

The invention relates to a synthesis method of (R)-(-)-1-methyl-3-amphetamine (I), and mainly solves the technical problems of complexity and high cost in existing synthesis methods of (R)-(-)-1-methyl-3-amphetamine compounds. According to the technical scheme of the invention, synthesis of the (R)-(-)-1-methyl-3-amphetamine compound comprises: a first step of reaction, i.e. taking phenylpropyl aldehyde as the raw material, subjecting the raw material to lewis acid catalyzed condensation reaction in a solvent, and then carrying out reaction with triphenylmethylamine to obtain benzyl triphenyl methyl imine (II); and a second step of reaction, reacting the compound II with a Grignard reagent in a solvent to obtain (R)-(-)-1-methyl-3-amphetamine, which is shown as the specification.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a method for synthesizing the key intermediate (R)-(-)-1-methyl-3-amphetamine of desrolol. Background technique [0002] Chiral aromatic amines are important intermediates in drug synthesis, and can also be used as chiral auxiliary agents and chiral resolving agents. In recent years, drugs, pesticides and fine chemicals containing chiral centers have received more and more attention in daily life and industrial and agricultural production. The chiral pharmaceutical industry is developing rapidly, and the single enantiomer drug is increasing at a rate of more than 20% every year. Chiral amines are important intermediates for the synthesis of neurological drugs, cardiovascular drugs, antihypertensive drugs, anti-infective drugs, and vaccines. Currently, 40% to 50% of chiral drugs are chiral amine compounds. [0003] (R)-(-)-1-methyl-3-amphetamine is the key intermediate of the an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/27C07C209/66
Inventor 陈芳军李书耘
Owner 湖南华腾制药有限公司
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