Synthetic method of 4-(N,N-dimethylamino) butyaldehyde dimethyl acetal

A technique for synthesizing butyraldehyde dimethyl acetal, which is applied in the field of synthesis of 4-(N,N-dimethylamino) butyraldehyde dimethyl acetal, and can solve the problems of troublesome processing, less than 20% yield, and high equipment requirements

Inactive Publication Date: 2008-11-19
STAR LAKE BIOSCI CO INC ZHAOQING GUANGDONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many methods for the synthesis of 4-(N,N-dimethylamino)butyraldehyde dimethyl acetal, but the results are not very satisfactory
This route involves a Grignard reaction that is very sensitive to water and air, which requires high equipment and is difficult to operate
Using 4-chloro-1-butanol as a raw material to prepare 4-(N,N-dimethylamino)butyraldehyde dimethyl acetal through oxidation, acetalization and ammonolysis is a relatively feasible way, the key is the Select, document (fine chemical industry, 2002,19 (7): 385-387) has described this method, and it has used PCC to make oxidizing agent, and when the inventor repeats operation with reference to document, oxidation reaction aftertreatment troubles, and yield is less than 20%. %

Method used

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  • Synthetic method of 4-(N,N-dimethylamino) butyaldehyde dimethyl acetal
  • Synthetic method of 4-(N,N-dimethylamino) butyaldehyde dimethyl acetal
  • Synthetic method of 4-(N,N-dimethylamino) butyaldehyde dimethyl acetal

Examples

Experimental program
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Effect test

Embodiment 1

[0014] Add 80g 4-chlorobutanol (w=80%), 700mL methylene chloride and oxidizing agent successively in 1000mL four-necked bottle to be 180g trichloroisocyanuric acid, N 2 Add dropwise catalyst 0.28g 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl free radical (also known as nitroxide free radical piperidinol) in 25mL dichloromethane under protection and ice-water bath cooling The solution in , stop dropping when the temperature of the system rises, continue to react for 1 to 3 hours, filter and wash with dichloromethane. The washing liquid and the filtrate were combined, and 100 mL of trimethyl orthoformate was added, and stirred at room temperature for 2 to 4 hours. Wash with 200mL of 2% sodium carbonate solution, dry over anhydrous magnesium sulfate, concentrate, and then distill under reduced pressure to obtain 32g of product.

[0015] Add 11g of 4-chlorobutyraldehyde dimethyl acetal obtained in the previous step, 30mL of 33% dimethylamine aqueous solution, 4.0g of sodium ca...

Embodiment 2

[0017] Add 80g 4-chlorobutanol (w=80%), 700mL methylene chloride and oxidizing agent successively in 1000mL four-necked bottle to be 200g trichloroisocyanuric acid, N 2 Add dropwise catalyst 0.38g 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl free radical (also known as nitroxide free radical piperidinol) in 25mL dichloromethane under protection and ice-water bath cooling The solution in , stop dropping when the temperature of the system rises, continue to react for 1 to 3 hours, filter and wash with dichloromethane. The washing liquid and the filtrate were combined, and 100 mL of trimethyl orthoformate was added, and stirred at room temperature for 2 to 4 hours. Wash with 200mL of 2% sodium carbonate solution, dry over anhydrous magnesium sulfate, concentrate, and then distill under reduced pressure to obtain 33g of product.

[0018] Add 11.2g of 4-chlorobutyraldehyde dimethyl acetal obtained in the previous step, 30mL of 33% dimethylamine aqueous solution, 4.0g of sodium ...

Embodiment 3

[0020] In the 1000mL four-necked bottle, add 80g 4-chlorobutanol (w=80%), 700mL methylene chloride and oxidizing agent successively to be 220g trichloroisocyanuric acid, N 2 Under protection and ice-water bath cooling, add dropwise catalyst 0.42g 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl radical (also known as nitroxide radical piperidinol) in 25mL dichloromethane The solution in , stop dropping when the temperature of the system rises, continue to react for 1 to 3 hours, filter and wash with dichloromethane. The washing liquid and the filtrate were combined, and 100 mL of trimethyl orthoformate was added, and stirred at room temperature for 2 to 4 hours. Wash with 200mL of 2% sodium carbonate solution, dry over anhydrous magnesium sulfate, concentrate, and then distill under reduced pressure to obtain 35g of product.

[0021] Add 11.2g of 4-chlorobutyraldehyde dimethyl acetal obtained in the previous step, 30mL of 33% dimethylamine aqueous solution, 4.0g of sodium carb...

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PUM

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Abstract

The invention discloses a method for synthesizing 4-(N, N- dimethylamino) butyaldehyde dimethyl acetal. The raw material of 4-chlorobutanol is subject to oxidation, aldolization and ammonolysis in sequence. In the process of the oxidation reaction, the used oxidizer is trichloride isocyanuric acid and the catalyst is 4-hydroxy-2,2,6,6-tetramethyl-1-Piperidinyloxy. The 4-(N, N- dimethylamino) butyaldehyde dimethyl acetal prepared by the method has high yield coefficient and purity quotient up to between 85 and 90 percent.

Description

technical field [0001] The invention relates to a method for synthesizing the intermediate 4-(N,N-dimethylamino)butyraldehyde dimethyl acetal for synthesizing tryptamine drugs. Background technique [0002] 4-(N,N-Dimethylamino)butyraldehyde dimethyl acetal is an intermediate in the synthesis of tryptamine drugs such as zomitriptan, sumatriptan and melatonin. There are many methods for the synthesis of 4-(N,N-dimethylamino)butyraldehyde dimethyl acetal, but the results are not ideal. Literature (J.Org.Chem., 1994, 59(17): 5076-5077) protects a hydroxyl group of 1,4-butanediol with p-toluenesulfonyl chloride, followed by oxidation, acetalization and chlorination. 4-Chlorobutyraldehyde dimethyl acetal has a long reaction route and a total yield of less than 20%. Literature (J.Org.Chem., 1994, 59(13): 3738-3741) starts from 4-chlorobutyryl chloride, and obtains the target intermediate through hydrogenation, acetalization and ammonolysis, and the reproducibility of this method...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C217/28C07C213/02
Inventor 何伟彪张逸伟林东恩伍文锋潘小锋
Owner STAR LAKE BIOSCI CO INC ZHAOQING GUANGDONG
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