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Monkine derivative and application thereof in preparation of high-optical-purity indoxacarb intermediate

A derivative and reaction technology, applied in the field of asymmetric catalytic synthesis, can solve the problems of uncertainty of catalytic performance, inability to catalyze reactions such as reaction efficiency, yield and enantioselectivity, and achieve good target product yield, The effect of high catalytic efficiency and low price

Active Publication Date: 2022-03-01
ANHUI GUANGXIN AGROCHEM
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although derivation based on the structure of cinchona has become a hot issue in order to provide a high-efficiency catalyst, according to the prior art reports and the inventor's experimental research results, the various catalysts developed based on the structure of cinchona, even if In the case of a very similar structure, it is still full of uncertainties in terms of catalytic performance such as reaction efficiency, yield and enantioselectivity (for example, referring to CN103333069A, CN108129306A, CN110511217A, etc.) in response to α-hydroxylation reactions, and even Because of the inability to catalyze the reaction (see "Research on Asymmetric Organocatalytic Oxidation Based on Drug Source Skeleton", Cai Yuanchun, Master's Thesis of Dalian University of Technology)

Method used

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  • Monkine derivative and application thereof in preparation of high-optical-purity indoxacarb intermediate
  • Monkine derivative and application thereof in preparation of high-optical-purity indoxacarb intermediate
  • Monkine derivative and application thereof in preparation of high-optical-purity indoxacarb intermediate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The preparation of embodiment 1 (S)-quinolin-4-yl ((1S, 2S, 4S, 5R)-5-vinylquinine-2-yl) methyl dimethylaminocarbonate (1a)

[0033] Under the protection of nitrogen, add 205ml of anhydrous THF and 10.0g (34.0mmol) cynicalin into a 1000ml three-necked glass bottle, cool to 5°C, add 60% NaH2.72g (54.7mmol) in batches, keep stirring for 30min, add DMCC dropwise 6.58g (61.2mmol), stirred at room temperature for 5h, then added 250g ice water, 400ml ethyl acetate, separated the water phase, extracted once with 200ml ethyl acetate, combined the ethyl acetate phase, dried with anhydrous MgSO4, filtered, evaporated the solvent , 200-300mesh silica gel column chromatography gave 7.45 g of a light yellow solid, with a yield of 60%. 1 HNMR (600MHz, CH 3OH-d4): δ8.84(t, J=6Hz, 1H), 8.31(d, J=6.0Hz, 1H), 8.08(d, J=6.0Hz, 1H), 7.80-7.78(t, J= 6Hz, 1H), 7.71-7.69(t, J=6Hz, 1H), 7.57(t, J=56Hz, 1H), 6.58(d, J=6.0Hz, 1H), 6.11-6.04(m, 1H), 5.14-5.11(m,2H),4.89(s,1H),3.40-3.36(m,1H),3...

Embodiment 2

[0034] Example 2 Preparation of (S)-quinolin-4-yl ((1S, 2S, 4S, 5R)-5-vinylquinine-2-yl) methylcyclohexylaminocarbonate (1b)

[0035] Add 205ml of anhydrous tetrahydrofuran and 10.0g (34.0mmol) cynclionin to a 1000ml three-necked glass bottle under nitrogen protection, cool to 5°C, add 60% NaH2.72g (54.7mmol) in batches, keep stirring for 30min, add ring Hexyl isocyanate 7.66g (61.2mmol), stirred at room temperature for 10h, then added 250g ice water, 400ml ethyl acetate, separated the water phase, extracted once with 200ml ethyl acetate, combined ethyl acetate phase, dried over anhydrous MgSO4, filtered, evaporated The solvent was removed, and 7.27 g of light yellow solid was obtained by 200-300 mesh silica gel column chromatography, with a yield of 51%. 1HNMR (600MHz, CH3OH-d4)::δ8.83(d, J=6.0Hz, 1H), 8.31(d, J=6.0Hz, 1H), 8.08(d, J=6.0Hz, 1H), 7.81- 7.79(t, J=6Hz, 1H), 7.71-7.68(t, J=9Hz, 1H), 7.59(d, J=6.0Hz, 1H), 6.58(d, J=6.0Hz, 1H), 6.20- 6.14(m,1H),5.13-5.11(m,2H),4....

Embodiment 3

[0036] Example 3 (S)-quinolin-4-yl ((1S,2S,4S,5R)-5-vinylquinine-2-yl)methyl-(3,4-dichloroanilino)carbonate Preparation of (1c)

[0037] Add 205ml of anhydrous tetrahydrofuran and 10.0g (34.0mmol) cynclionin to a 1000ml three-neck glass bottle under nitrogen protection, cool to 5°C, add 60% NaH2.72g (54.7mmol) in batches, keep stirring for 30min, add dropwise 3 , 11.5g (61.2mmol) of 4-dichlorophenylisocyanate, stirred at room temperature for 10h, then added 250g of ice water, 400ml of ethyl acetate, separated the water phase, extracted once with 200ml of ethyl acetate, combined the ethyl acetate phase, and anhydrous MgSO4 was dried, filtered, the solvent was distilled off, and 7.54 g of a light yellow solid was obtained by 200-300 mesh silica gel column chromatography, with a yield of 46%. 1H-NMR (600MHz, CH3OH-d4): δ8.85(d, J=6.0Hz, 1H), 8.37(d, J=6.0Hz, 1H), 8.09(d, J=6.0Hz, 1H), 7.81 -7.64(m,1H),7.38(d,J=6.0Hz,1H),7.33(t,J=12.0Hz,1H),6.66(d,J=6.0Hz,1H),6.16(s,1H) ,5.12(m...

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Abstract

The invention discloses a novel cinchona alkaloid, namely a novel cinchona derivative, which is easy to prepare, low in cost and high in efficiency. The novel cinchona alkaloid is prepared by amidation derivatization of hydroxyl at C-9 site of cinchona. The catalytic efficiency, the target product yield and the enantiomer selectivity of cinchonine and other cinchona alkaloid organic catalysts in the asymmetric alpha-hydroxylation reaction of the 5-chloro-1-indanone-2-methyl formate intermediate are greatly improved. The content of the S isomer of the 5-chloro-2-methoxycarbonyl-2-hydroxy-1-indanone is increased to 90% or above from 50% when cinchonin is used as the catalyst, and the catalyst disclosed by the invention is simple in synthesis process, small in dosage and low in cost, and is beneficial to industrial production and provision of a high-quality indoxacarb product.

Description

technical field [0001] The invention belongs to the technical field of asymmetric catalysis synthesis, and specifically relates to a novel cynclionin derivative and its application in the preparation of highly optically pure indoxacarb intermediates. Background technique [0002] Indoxacarb (Indoxacarb) is a carbamate insecticide with an oxadiazine structure developed by DuPont. Its molecule contains a chiral C atom and has two configurations, R and S, but only S-configuration Has insecticidal activity. Among the indoxacarb products currently sold in the global market, the S / R ratios are 1 / 1 (racemate), 3 / 1, 9 / 1 and 99.1 (high-end products), and the demand is about 3500 tons / year, while the production capacity can only reach 1500 tons / year, and the current production technology is also relatively backward, which limits the possibility of expanding its production capacity. Therefore, the development of high-efficiency indoxacarb products (high optical purity) has important e...

Claims

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Application Information

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IPC IPC(8): C07D453/04C07C67/31C07C69/757B01J31/02
CPCC07D453/04B01J31/0245B01J31/0271B01J31/0244C07C67/31B01J2231/70C07C2602/08C07B2200/07C07C69/757
Inventor 寿王鸽王震宇余吉张晓琴
Owner ANHUI GUANGXIN AGROCHEM