Compound, preparation method thereof and application of compound in preparation of bicyclopyrone intermediate

A compound and solvate technology, applied in the preparation of organic compounds, chemical instruments and methods, preparation of carboxylic acid esters, etc., can solve the problems of incomplete reaction of raw materials, achieve large-scale production, less by-products, and reduce side reactions Effect

Active Publication Date: 2022-07-08
SHANDONG WEIFANG RAINBOW CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0026] In the present invention, the two fragments of nicotinic acid are first docked under the action of alkali to generate intermediate I, and then through intramolecular ring closure of ammonium salt, which can significantly improve the yield of flupidalone intermediate (II) and reduce side effects. The reaction overcomes the defect that the prior art (for example, the methods reported in WO2006059103A2 and WO2004078729A1) directly leads to incomplete reaction of raw materials through ammonium salt molecular ring closure

Method used

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  • Compound, preparation method thereof and application of compound in preparation of bicyclopyrone intermediate
  • Compound, preparation method thereof and application of compound in preparation of bicyclopyrone intermediate
  • Compound, preparation method thereof and application of compound in preparation of bicyclopyrone intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0148] Ethyl 2-methyl-6-(trifluoromethyl)nicotinate (intermediate Synthesis of A) (an example of route A-1)

[0149]

[0150] Step 1: Synthesis of Intermediate IA (enol formula Ia-1; keto formula Ib-1)

[0151] Add ethyl acetoacetate (6 g, 46.5 mmol) and 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (8 g, 47.6 mmol) to a single-necked flask, and cool in an ice-water bath. The ethanol solution of sodium ethoxide (56 mmol) was slowly added, the dropwise addition was completed, the mixture was stirred at 0° C. for 2 hours, and monitored by thin layer chromatography (TLC) until the reaction was completed. The reaction solution was poured into 50 mL of dilute hydrochloric acid, extracted three times with ethyl acetate (60 mL × 3), the organic phases were combined, washed with saturated brine, the organic phase was separated, concentrated to obtain 11.96 g of brown liquid, which was purified by column chromatography for analysis The samples were analyzed by NMR H and C spectra, and t...

Embodiment 2

[0161] Ethyl 2-chloromethyl-6-(trifluoromethyl)nicotinate (intermediate B) Synthesis

[0162]

Embodiment 2-1

[0164] Synthesis of intermediate IB (enol formula Ia-2; keto formula Ib-2)

[0165] Into a 250 mL four-necked flask, anhydrous ethanol (20 g) and ethyl 4-chloroacetoacetate (3.46 g, 21 mmol) were added, and 4-ethoxy-1,1,1-trifluorobut-3-ene was added under stirring -2-one (3.36 g, 20 mmol). The temperature was lowered to -15°C, and sodium ethoxide (2.04 g, 30 mmol) dissolved in ethanol was slowly added dropwise, and the dropwise addition was completed in about 1.0 hours. Incubate at -15°C for about 2.0 hours, and monitor by thin layer chromatography (TLC) until the end of the reaction. The reaction solution was poured into 30 mL of diluted hydrochloric acid, and the ethanol was removed by rotary evaporation. The aqueous phase was extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, dried over anhydrous magnesium sulfate, rotary evaporated and concentrated to obtain crude product 4.25 g, the yield is 54.3%.

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Abstract

The invention discloses a compound and a preparation method thereof, and an application of the compound in preparation of a bicyclopyrone intermediate, and a bicyclopyrone intermediate II can be prepared with high yield through an intermediate I (a compound with a structural formula shown as a formula (Ia) and / or a formula (Ib)) or a pharmaceutically acceptable salt, a solvate and a tautomer thereof. According to the invention, the two compounds are firstly butted under the action of alkali to generate the intermediate I, and then the intermediate I is subjected to ring closing in an ammonium salt molecule, so that the yield of the bicyclopyrone intermediate (II) can be remarkably improved, side reactions are reduced, and the defect of incomplete reaction of raw materials caused by direct ring closing through the ammonium salt in the prior art is overcome. According to the fractional step method, the intermediate I is generated under the action of alkali, and the bicyclopyrone intermediate (II) is generated through the ring closing reaction, so that side reactions can be reduced, and the yield can be increased.

Description

technical field [0001] The present invention relates to the technical field of pesticides, in particular to a compound and a preparation method thereof, as well as its application in the preparation of an intermediate of flufenox. Background technique [0002] In 2015, diflufenazone was launched for the first time, and it has been registered and listed in the United States, Canada, Argentina, Uruguay, Australia and other countries. Fluoxazone is a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, which causes the destruction of chlorophyll in plants. A variety of herbicides such as cyclosulfonone and pyrasulfatole are compounded. The selective herbicide variety has good activity against broadleaf weeds and perennial annual weeds, and can be used in corn, wheat, barley, sugarcane and other crop fields. The structure of flufenox is as follows: [0003] [0004] The method reported by the current typical process (patent CN1824662B) of flufenox is as follows: [0005]...

Claims

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Application Information

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IPC IPC(8): C07C69/738C07C67/343C07D213/80C07D213/803
CPCC07D213/80C07D213/803C07C67/31C07C41/26C07C43/13C07C69/716C07C69/734
Inventor李志清宫风华张海潮张洪全邱瀟杨
OwnerSHANDONG WEIFANG RAINBOW CHEM