Preparation method of aza-bicyclic [2, 2, 1] hepta-5-alkene-3-ketone

A technology of azabicyclo and cyclopentadiene, which is applied in the field of preparation of azabicyclo[2,2,1]hept-5-en-3-one, can solve the problem of low yield and achieve simplified operation process, increase reaction yield, and reduce pollution

Inactive Publication Date: 2018-03-16
四平市精细化学品有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite multiple extractions, the loss of the aqueous phase is still an important reason for the relatively low yield of the current product

Method used

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  • Preparation method of aza-bicyclic [2, 2, 1] hepta-5-alkene-3-ketone

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preparation example Construction

[0024] The invention provides a preparation method of azabicyclo[2,2,1]hept-5-en-3-one, comprising:

[0025] S1) In the presence of cross-linked polystyrene sodium sulfinate, mix and react 1,3-cyclopentadiene and cyanide to obtain a bicyclic compound;

[0026] S2) Hydrolyzing the bicyclic compound to obtain azabicyclo[2,2,1]hept-5-en-3-one.

[0027] Wherein, the sources of all the raw materials in the present invention are not particularly limited, as long as they are commercially available.

[0028] In the presence of cross-linked polystyrene sodium sulfinate, 1,3-cyclopentadiene and cyanide are mixed and reacted; Sodium polystyrene sulfinate can be used without any special limitation. It is a solid-loaded sodium sulfinate reagent obtained by polymerizing and cross-linking sodium vinylbenzene sulfinate; the cross-linked polystyrene The loading capacity of sodium ethylene sulfinate is preferably 1 to 2 mequiv / g, more preferably 1.1 to 1.8 mequiv / g, and more preferably 1.1 to...

Embodiment 1

[0037] In a 1000mL three-necked bottle with a thermometer and an exhaust gas absorption device, add 500ml of methanol, 50g of cross-linked polystyrene sodium sulfinate and 5.0g of cyclopentadiene, control the low temperature at 0-5°C, and slowly pass the Inject 2.5g of cyanogen chloride gas, and simultaneously add dropwise 5% sodium hydroxide alcohol solution to control the pH value between 4 and 5. After the dropwise addition was completed, the reaction was continued for 8 hours. The solid was isolated by filtration.

[0038] Add this solid to 100ml of 5% alcohol solution of acetic acid, continue to react at room temperature for 8 hours, filter off the solid catalyst particles, concentrate the filtrate, and precipitate a white crystal product, which is azabicyclo[2,2,1]hept-5-ene -3-ketone, the product quality is 4.21g, the yield is 95% (relative to cyanogen chloride), and the purity is 99.5%.

[0039] The reaction flow diagram of embodiment 1 is as figure 1 shown.

[004...

Embodiment 2

[0041] The recycling of embodiment 2 catalysts is reused

[0042] Catalyst recovery: Soak the filtered solid catalyst particles in 10% sodium hydroxide aqueous solution for 12 hours, filter and separate the catalyst particles.

[0043] Reuse of the reaction solution in Example 1: Add the recovered catalyst particles into the solvent after the reaction in Example 1, add 5.0 g of cyclopentadiene, and control the low temperature to 0-5°C. Slowly feed 2.5 g of cyanogen chloride gas, and at the same time add dropwise 5% sodium hydroxide alcohol solution to control the pH value between 4 and 5. After the dropwise addition was completed, the reaction was continued for 8 hours. The solid was isolated by filtration. This solid was added to 100ml of 5% alcohol solution of acetic acid, and the reaction was continued at room temperature for 8 hours. The solid catalyst particles were filtered off, the filtrate was concentrated, and a white crystal product was precipitated. The product q...

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Abstract

The invention provides a preparation method of aza-bicyclic [2, 2, 1] hepta-5-alkene-3-ketone. The preparation method includes the steps: S1) performing hybrid reaction on 1, 3-cyclopentadiene and cyanide under the condition of presence of crosslinked polystyrene sulfinic acid sodium to obtain a bicyclic compound; S2) hydrolyzing the bicyclic compound to obtain the aza-bicyclic [2, 2, 1] hepta-5-alkene-3-ketone. Compared with the prior art, the crosslinked polystyrene sulfinic acid sodium serves as a polymer-immobilized catalyst and can be recycled, the reaction post-treatment operation process is simplified, only simple filtration is needed, reaction yield is improved, cost is reduced, and environmental pollution is decreased.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of azabicyclo[2,2,1]hept-5-en-3-one. Background technique [0002] Abacavir is a major human immunodeficiency virus reverse transcriptase inhibitor. Because of its strong anti-in vitro activity, good bioavailability, and easy penetration into the central nervous system, it is currently the main anti-AIDS drug. Abacavir can be conveniently synthesized through the intermediate azabicyclo[2,2,1]hept-5-en-3-one. [0003] At present, the synthetic route of intermediate azabicyclo[2,2,1]hept-5-en-3-one usually includes two unit reaction processes, that is, diene (cyclopentadiene) and dienophile (cyanide ) to form a bicyclic compound through a Diels-Alder reaction, and then hydrolyze to obtain the product. In order to improve the yield of the Diels-Alder cyclization reaction, sulfinic acid derivatives are usually used as catalysts, and first...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/52B01J31/06
CPCB01J31/06B01J2231/326C07D209/52Y02P20/584
Inventor 薛李冰刘长宝高航王春艳刘丽娟罗冬琦
Owner 四平市精细化学品有限公司
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