(S)1-phenyl-1,2,3,4-tetrahydroisoquinoline synthesis method

A technology of tetrahydroisoquinoline and a synthesis method is applied in the field of synthesis of 1-phenyl-1,2,3,4-tetrahydroisoquinoline, and can solve the problems of poor optical purity and low yield of the product, To achieve the effect of simple and safe reaction operation, easy access to raw materials and simple equipment

Active Publication Date: 2020-01-14
ENANTIOTECH CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method not only has a low yield, but also has poor

Method used

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  • (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline synthesis method

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Example Embodiment

[0018] The embodiment of the present invention provides a method for synthesizing (S) 1-phenyl-1,2,3,4-tetrahydroisoquinoline, and the reaction route of the synthesis method includes:

[0019]

[0020] The synthesis method includes the following steps:

[0021] 1) Dissolve raw material 1 in a solvent, add alkali and catalyst;

[0022] 2) Using hydrogen for gas replacement to form a hydrogen atmosphere, and performing a pressurized reaction to obtain (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline 2;

[0023] Wherein, the catalyst is a BIAMH system catalyst, a D-BIMAH system catalyst or a P-BIMAH system catalyst.

[0024] In the above synthesis method, the general structural formula of the BIAMH system catalyst used is:

[0025]

[0026] The general structural formula of D-BIMAH system catalyst is:

[0027]

[0028] The general structural formula of the P-BIMAH system catalyst is:

[0029] Where R 1 It is a high molecular polymer.

[0030] Preferably, in step 2), the catalyst is a P-BIMAH system...

Example Embodiment

[0042] Example 1

[0043] In this embodiment, a method for synthesizing (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline, the steps are as follows:

[0044] 1) In a 5L autoclave, under an argon atmosphere, add 100g of the raw material reactant 1-phenyl-dihydroquinoline (1) from the feed port, then add 1L of ethanol to fully dissolve the raw material (1), and continue to pass Enter argon for bubbling and degassing, bubbling continuously for 1 hour, and the degassing is completed;

[0045] 2) Then under an argon atmosphere, add 0.5g of catalyst (S)-diopRuCl from the feeding port 2 (R)-P-Me-BIMAH (purchased from Zhongshan Yiantai Pharmaceutical Technology Co., Ltd.), add 12g of potassium tert-butoxide, quickly close the feeding port after the feeding is completed; replace the argon with hydrogen, and slowly introduce hydrogen to 30atm, Close the inflation valve and stir the reaction at 25-35°C; when the pressure drops to remain unchanged, the reaction is deemed to have stopped, and samples a...

Example Embodiment

[0047] Example 2

[0048] This embodiment is a method for synthesizing (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline. The steps are the same as those in embodiment 1, except that the catalyst used is (S)-diopRuCl 2 (R)-Me-BIMAH (BIAMH system catalyst).

[0049] Specific steps are as follows:

[0050] 1) In a 5L autoclave, under an argon atmosphere, add 100g of the raw material reactant 1-phenyl-dihydroquinoline (1) from the feed port, then add 1L of ethanol to fully dissolve the raw material (1), and continue to pass Enter argon for bubbling and degassing, bubbling continuously for 1 hour, and the degassing is completed;

[0051] 2) Then under an argon atmosphere, add 0.5g of catalyst (S)-diopRuCl from the feeding port 2 (R)-Me-BIMAH (purchased from Zhongshan Yiantai Pharmaceutical Technology Co., Ltd.), finally add 12g potassium tert-butoxide, after the addition is complete, quickly close the feeding port; replace the argon with hydrogen, slowly pass in hydrogen to 30atm, and close Sti...

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Abstract

The invention relates to a (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline synthesis method, wherein the reaction route is defined in the specification. The synthesis method comprises: 1) dissolving a rawmaterial 1 in a solvent, and adding an alkali and a catalyst; and (2) carrying out gas replacement by using hydrogen to form a hydrogen atmosphere, and carrying out an pressurization reaction to obtain (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline 2, wherein the catalyst is a BIAMH system catalyst, a D-BIMAH system catalyst or a P-BIMAH system catalyst.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a synthesis method of (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline. Background technique [0002] Sophinacin is a selective muscarinic M3 receptor antagonist developed by Japan Astellas Company, mainly used for the treatment of overactive bladder with symptoms of urgency and frequent urination. The chemical name of Sofinaxin is (3R)-1-azabicyclo[2,2,2]octane-3-yl(1S)-1-phenyl-1,4-dihydroisoquinoline- 2-(1H)-carboxylate, the structure is shown in the following formula (1): [0003] [0004] It can be seen from the above structural formula that solifenacin contains two chiral centers, one chiral center is located on the isoquinoline (2) structural unit, and the other chiral center is located on the quinuclidin structural unit. Therefore the synthetic method of solifenacin is usually based on (S) 1-phenyl-1,2,3,4-tetrahydroisoquinoline (formula (2)) and quinuclidinol (f...

Claims

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Application Information

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IPC IPC(8): C07D217/02
CPCC07B2200/07C07D217/02
Inventor 李彦雄蒙发明温锦涛李苏泳郭俊毛波徐亮
Owner ENANTIOTECH CORP
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