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Method for preparing chiral diaryl- substitute methylamine

A technology of diaryl and aryl formaldehyde, which is applied in the field of preparation of chiral diaryl substituted methylamine, can solve the problems of low yield and high cost of raw and auxiliary materials, achieve high yield, reduce production cost and reduce emissions Effect

Active Publication Date: 2015-04-15
HEBEI BOLUNTE PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to solve the problems of low yield and high cost of raw and auxiliary materials existing in the current chiral amine synthesis process, including the original research process and various improved methods disclosed later, and to provide a high-purity, high-yield, production Preparation method of chiral diaryl-substituted methylamine with low cost and low three-waste discharge

Method used

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  • Method for preparing chiral diaryl- substitute methylamine
  • Method for preparing chiral diaryl- substitute methylamine
  • Method for preparing chiral diaryl- substitute methylamine

Examples

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Embodiment 1

[0039] Embodiment 1: Preparation of (1,5-cyclooctadiene) rhodium chloride dimer

[0040] In a 250 ml dry three-necked round-bottom flask, add an electromagnetic stirrer and 60 ml of absolute ethanol, pass high-purity nitrogen gas for 20 minutes to release the oxygen dissolved in the ethanol, and then add 10 g (0.038 mol) rhodium trichloride Trihydrate, 8 g (0.075 mol) of anhydrous sodium carbonate and 5.7 g (0.053 mol) of 1,5-cyclooctadiene, the temperature was raised to 55~60°C, and the reaction was kept for 8 hours, and the conversion was complete. Remove the inorganic salt by filtration, dry the organic phase and evaporate to dryness to obtain a yellow solid, which is recrystallized in isopropanol to obtain 10.6 g of an orange solid, which is the product (1,5-cyclooctadiene) rhodium chloride dimer . The yield based on rhodium trichloride trihydrate was 82.8%.

Embodiment 2

[0041] Embodiment 2: Preparation of (1,5-cyclooctadiene) rhodium chloride dimer

[0042]In a 100 ml dry three-neck round-bottom flask, add an electromagnetic stirrer and 30 ml of anhydrous methanol, pass through argon for 20 minutes to release the oxygen dissolved in methanol, and then add 5 g (0.019 mol) of rhodium trichloride Hydrate, 5.25 g (0.038 mol) of anhydrous potassium carbonate and 10.2 g (0.094 mol) of 1,5-cyclooctadiene, the temperature was raised to 65°C, and the reaction was refluxed for 12 hours, and the conversion was complete. Remove the inorganic salt by filtration, dry the organic phase and evaporate to dryness to obtain a yellow solid, which is recrystallized in isopropanol to obtain 5.4 g of an orange solid, which is the product (1,5-cyclooctadiene) rhodium chloride dimer . The yield based on rhodium trichloride trihydrate was 84.5%.

Embodiment 3

[0043] Embodiment 3: Preparation of (1,5-cyclooctadiene) rhodium chloride dimer

[0044] Other conditions are the same as in Example 2, except that the amount of 1,5-cyclooctadiene is 2.04 g (0.019 mol), and 4.9 g of the product (1,5-cyclooctadiene) rhodium chloride dimerization is obtained as an orange solid body. The yield based on rhodium trichloride trihydrate is 76.7%.

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Abstract

The invention discloses a method for preparing chiral diaryl-substitute methylamine. The method comprises the following steps of: performing condensation on aryl-formaldehyde as a raw material and sulfonic acid amide to obtain an imine midbody; then, reducing with an aryl-boric acid under the action of a chiral rhodium catalyst to obtain a chiral intermediate product N-[ bi-substitute-methyl] sulfonic acid amide; and then, performing reducing deprotection to obtain the chiral diaryl-substitute methylamine, wherein the chiral rhodium catalyst is prepared by performing a reaction on (1,5-cyclooctadiene) rhodium chloride dimer and (R)-1,1'-binaphthol phosphorus imide. The method for preparing the chiral diaryl-substitute methylamine is characterized in that by adopting the chiral rhodium catalyst, highly selective catalytic reduction is realized, and the high-yield amine chiral intermediate product is obtained. One of the applications of the chiral diaryl- substitute methylamine is that as the intermediate product of an anti-allergic drug-Levocetirizine, the chiral diaryl-substitute methylamine is further synthesized into chiral piperazine, and then, substitution and hydrolysis are performed to obtain the Levocetirizine. The method for preparing the chiral diaryl-substitute methylamine has the advantages that the yield of the whole synthesis step is high, the discharge of the three wastes is low, and the process route is feasible. The method for preparing the chiral diaryl-substitute methylamine has industrial application value.

Description

technical field [0001] The invention relates to a preparation method of a chiral diaryl-substituted methylamine, one of the chiral diaryl-substituted methylamines can be used as an intermediate of levocetirizine and various medicines. technical background [0002] Cetirizine has the strongest drug activity among the second-generation antihistamines, and it has good anti-inflammatory and anti-allergic effects and the highest bioavailability. Although the central nervous system activity of cetirizine is very light, there are still adverse reactions such as drowsiness. Studies have shown that this is mainly due to the certain affinity between the D-body and the receptors in the brain. And its single optical isomer, levocetirizine, is a selective H1 receptor antagonist and a third-generation antihistamine. Because it has no central nervous system side effects such as sedation and drowsiness, and its antihistamine activity is equivalent to that of cetirizine, it is gradually pr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07B53/00C07C209/68C07C211/29C07C211/27C07C213/08C07C217/58B01J31/22
Inventor 李玮张敬栓焦招招程喜伟宋洁洁
Owner HEBEI BOLUNTE PHARMA
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