Chiral organic small molecular compound of S-prolinol having cyclopropane structure and synthetic method of chiral organic small molecular compound

A small molecular compound, prolinol technology, applied in the preparation of organic compounds, organic compound/hydride/coordination complex catalysts, organic chemistry, etc., can solve the problem of high reagent cost, harsh process conditions, enantiomer Low structural selectivity and other issues, to achieve the effect of simple operation, reasonable process and low cost

Inactive Publication Date: 2013-12-11
JIAXING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] In this synthetic route, the yield of products reduced to olefins is low, the cost of reagents is high, and the requirements for process conditions are harsh. During the cyclization process, the enantiomeric selectivity is low (structure A: structure B = 1:4) Need further chiral preparation and resolution, not suitable for large-scale industrial production

Method used

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  • Chiral organic small molecular compound of S-prolinol having cyclopropane structure and synthetic method of chiral organic small molecular compound
  • Chiral organic small molecular compound of S-prolinol having cyclopropane structure and synthetic method of chiral organic small molecular compound
  • Chiral organic small molecular compound of S-prolinol having cyclopropane structure and synthetic method of chiral organic small molecular compound

Examples

Experimental program
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Effect test

Embodiment 1

[0055] (1S, 3S, 5S)-N-tert-butoxycarbonyl-2-azabicyclo[3,1,0]hexane-3-ethyl carboxylate 1 and (1R, 3S, 5R)-N-tert-butoxy Preparation of ethyl carbonyl-2-azabicyclo[3,1,0]hexane-3-carboxylate 2

[0056] in N 2 Under protection, (S)-1-N-tert-butoxycarbonyl-2,3-dihydro-2-pyrrole carboxylic acid ethyl ester (provided by Shanghai Tongchang Biomedical Technology Co., Ltd., CAS) was added to a dry 250ml two-necked reaction flask No.: 178172-26-4) (34.0g, 0.13mol) was dissolved in 200ml of dichloromethane (DCM), cooled to -15°C, and diethylzinc (Et 2 Zn) (1.2eq, 0.17mol), stirring reaction 0.5h after completion of dropwise addition, dropwise addition of chloroiodomethane (CH 2ClI) (1.1eq, 0.15mol) in dichloromethane (DCM) solution, insulated at -15°C and stirred for 24h, after the reaction was completed, the reaction was quenched with an aqueous solution of 13% ethylenediaminetetraacetic acid (EDTA) with a concentration of 13% by mass , heated to 25°C, stirred for 2 hours, stood st...

Embodiment 2

[0065] Preparation of (1S, 3S, 5S)-N-tert-butoxycarbonyl-2-azabicyclo[3,1,0]hexane-3-methanol 3

[0066] The three-necked reaction flask was added with (1S, 3S, 5S)-N-tert-butoxycarbonyl-2-azabicyclo[3,1,0]hexane-3-carboxylate ethyl ester prepared in Example 1, namely compound 1 ( 25.5g, 0.10mol), add anhydrous tetrahydrofuran to dissolve, control the temperature at 20°C, add lithium aluminum tetrahydrogen (LiAlH 4 ), added 3.8 g (0.10 mol) of lithium aluminum tetrahydrogen in total, then kept the temperature at 20° C. and stirred for 4 hours, concentrated tetrahydrofuran under reduced pressure, added 1% dilute hydrochloric acid dropwise after concentration, separated the upper organic layer, and added Add dichloromethane (DCM), then stir for 10-20 minutes, remove the lower organic layer, add dichloromethane (DCM) to the water layer, remove the lower organic layer, combine the organic layers, and wash with an appropriate amount of anhydrous sodium sulfate Dry and continue to ...

Embodiment 3

[0071] Preparation of (1R,3S,5R)-N-tert-butoxycarbonyl-2-azabicyclo[3,1,0]hexane-3-methanol 5

[0072] The three-necked reaction flask was added with (1R, 3S, 5R)-N-tert-butoxycarbonyl-2-azabicyclo[3,1,0]hexane-3-ethyl carboxylate prepared in Example 1, namely compound 2 ( 2.55g, 0.01mol), add anhydrous tetrahydrofuran to dissolve, control the temperature at 20°C, add lithium aluminum tetrahydrogen (LiAlH 4 ), add 0.38g (0.01mol) of lithium tetrahydrogen aluminum, then keep the temperature at 20°C and stir for 4 hours, concentrate the tetrahydrofuran under reduced pressure, add 1% dilute hydrochloric acid dropwise after the concentration, remove the upper organic layer, and refill the water layer Add dichloromethane (DCM), then stir for 10-20 minutes, remove the lower organic layer, add dichloromethane (DCM) to the water layer, remove the lower organic layer, combine the organic layers, and wash with an appropriate amount of anhydrous sodium sulfate Dry and continue to concen...

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Abstract

The invention provides a chiral organic small molecular compound of S-prolinol having a cyclopropane structure and a synthetic method of the chiral organic small molecular compound. The synthetic method provided by the invention comprises the following steps: (1), carrying out a Simmons-Smith cyclopropane reaction on (S)-1-N-t-butyloxycarboryl-2,3-dihydro-2-pyrrole ethyl formate; (2), carrying out an ester reduction reaction on the reaction product obtained in the step (1); and (3), carrying out an amino elimination protective reaction of the reaction product obtained in the step (2) so as to obtain the chiral organic small molecular compound of the S-prolinol having the cyclopropane structure. The method provided by the invention is reasonable in process, simple to operate and low in cost; an enantiomer product having optical purity can be obtained without further chiral preparation and separation; the synthetic method provided by the invention is an ideal method for synthesizing the chiral organic small molecular compound of the S-prolinol having the cyclopropane structure; the S-prolinol having the cyclopropane structure can be used as a chiral catalyst applied in a plurality of asymmetric catalytic reactions.

Description

technical field [0001] The invention relates to the technical field of compound preparation, in particular to a novel S-prolinol chiral organic small molecule compound with a cyclopropane structure and a synthesis method thereof. Background technique [0002] The asymmetric reaction catalyzed by organic small molecule compounds has developed rapidly in the past ten years, and has become the third type of potential asymmetric synthesis method that has the same status as organometallic catalysis and enzyme catalysis. However, most of the existing organic small molecular compounds use cheap and easy-to-obtain natural products as chiral sources, and their structural types are limited. On the premise of not changing its catalytic activity, there are certain limitations in the modification of its structure and the realization of structural diversity, which leads to problems such as fewer types of catalytic reactions and limited universality of catalytic reactions. [0003] Carril...

Claims

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Application Information

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IPC IPC(8): C07D209/52B01J31/02C07C205/44C07C201/12
Inventor 余焓张俊勇谢景力
Owner JIAXING UNIV
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