CN110105349A - The synthetic method and its application of topramezone impurity - Google Patents

Abstract

The invention discloses a method for synthesizing oxaflutole impurities. Using 2,3-dimethylaniline as a starting material, 3-[3-[3-[3 ‑Bromo‑2‑methyl‑6‑(methylsulfonyl) phenyl]‑4,5‑dihydroisoxazole, condensed with 1‑methyl‑5‑hydroxypyrazole under alkaline conditions to synthesize 3-[2-methyl-3-(1-methyl-1H-pyrazole-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole; this The invention also discloses an application of the corresponding product. The synthesis method provided by the invention is simple to operate, the process is easy to control, the yield of the obtained product is 40% to 80%, and the prepared product can be used as a standard product for detecting and monitoring the synthesis of oxaflutole.

Description

Synthesis method and application of oxaflutole impurity

technical field

The invention belongs to the field of pharmacy and relates to a method for synthesizing the impurities of the pesticide oxaflutole, namely 3-[2-methyl-3-(1-methyl-1H-pyrazole-5-oxyl)-6-( Synthetic method of methylsulfonyl)phenyl]-4,5-dihydroisoxazole and application of corresponding synthetic products.

Background technique

In the production process of drugs, the formation of impurities is often accompanied, which not only affects the yield of products, but also affects the quality of drugs, which in turn affects the use of drugs. Effective monitoring of impurities during synthesis plays a key role in ensuring product quality, yield, and reducing the impact of impurities on drug effectiveness.

Topramezone, chemical name: [3-(4,5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl]-(5 -Hydroxy-1-methyl-1H-pyrazol-4-yl)methanone, pure white powder solid, molecular formula: C ₁₆ H ₁₇ N ₃ O ₅ S, molecular weight: 363.39. The structure is as follows:

Oxaflutole is a new type of 4-hydroxyphenylpyruvate dioxidase (HPPD) inhibitor newly developed and marketed by BASF, Germany, as a post-emergence herbicide in corn fields. It can hinder the synthesis of carotenoids and the photosynthesis of chloroplasts, and eventually lead to the death of weeds containing HPPD enzymes. It has good selectivity for the vast majority of corn, including conventional corn, sweet and waxy corn, and currently has the best safety for corn.

And in the current industrial production, the following synthetic route will be utilized to synthesize oxaflutole:

The synthetic route of oxaflutole

During the synthesis using the above synthetic route, it was found that in polar aprotic solvents, 1-methyl-5-hydroxypyrazole and 3-[3-bromo-2-methyl-6-(methylsulfonyl ) Phenyl]-4,5-dihydroisoxazole easily undergoes a substitution reaction on the benzene ring under alkaline conditions, resulting in 3-[2-methyl-3-(1-methyl-1H-pyridine) oxazole-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole. 3-[2-Methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisooxane generated above azole directly affects the synthesis yield of oxaflutole, and there is no relevant report on this impurity in the previous literature, so the prior art does not provide measures to control the reaction conditions and avoid the generation of 3-[2-methyl -3-(1-Methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide an impurity of oxaflutole, namely 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methyl) Synthesis of sulfonyl)phenyl]-4,5-dihydroisoxazole starting with 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5- Dihydroisoxazole was condensed with 1-methyl-5-hydroxypyrazole under basic conditions to synthesize 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl )-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole. The synthesis method is simple in process, easy to control, and the yield is 40-80%.

Another object of the present invention is to provide 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl prepared above An application of ]-4,5-dihydroisoxazole. As a standard, it can be used to detect and monitor the synthesis of oxaflutole.

For solving the above-mentioned technical problems, the technical scheme adopted in the present invention is:

A kind of synthetic method of oxaflutole impurity, described impurity is 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methylsulfonyl) Phenyl]-4,5-dihydroisoxazole, its synthetic method comprises the following steps that are carried out in turn:

1) Preparation of raw materials, including preparation of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole and 1-methyl-5-hydroxypyridine azole, wherein the preparation method of the 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole is to use 2,3-dimethyl Aniline was used as the starting material, and 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4 was synthesized through methyl sulfide, bromination, oxidation, oxime formation, and chlorination ring closure, 5-dihydroisoxazole;

The synthetic method of the 1-methyl-5-hydroxypyrazole is to synthesize 1-methyl-5-hydroxypyrazole by reacting methyl 3-methoxyacrylate and methylhydrazine;

2) Condensation reaction

The prepared 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole was mixed with 1-methyl-5-hydroxypyrazole in basic Condensation reaction occurs under the conditions, and finally 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4 is prepared, 5-Dihydroisoxazole.

In the above reaction, the synthetic route of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole is:

.

The synthetic route of 1-methyl-5-hydroxypyrazole is as follows:

.

And then the synthetic route of the present invention is:

.

As a limitation to step 2) in the present invention: The step 2) is performed in the following sequence of steps:

①Add catalyst base and 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole to solvent A and dissolve to obtain solution B. The solution B was heated to 80～150°C;

② Dissolve 1-methyl-5-hydroxypyrazole in solvent A, add dropwise to the reaction flask, mix with solution B, and complete the reaction at the temperature of step ①, and obtain reaction solution C after the reaction is completed;

3. The reaction solution C was lowered to room temperature and poured into ice water, extracted with ethyl acetate or dichloromethane, the organic phase was washed with water, and then concentrated to obtain 3-[2-methyl-3-(1-methyl-1H -Pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole.

As the limitation to step 1 in the present invention: the catalyst base in the step 1 is any one in sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide, and the consumption of the base is the same as that of 3-[3-bromo- The molar equivalent ratio of the amount of 2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole is 0.5-5:1.

As a limitation to the solvent A in the present invention: the solvent A used in the steps ① and ② is any one of DMF, DMAC and NMP.

As another limitation of the present invention: the 1-methyl-5-hydroxypyrazole is combined with 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5- The molar equivalent ratio of the amount of dihydroisoxazole is 1-1.5:1.

The present invention also provides a 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5- Application of dihydroisoxazole, the 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4 , 5-Dihydroisoxazole was used as a standard to detect and monitor the synthesis of oxaflutole.

Compared with the prior art, the present invention has the following advantages: the present invention provides impurities generated in the production process of oxaflutole: 3-[2-methyl-3-(1-methyl-1H-pyrazole) The reaction process and reaction conditions of -5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole, according to the above reaction, it can be known that 3-

Conditions required for [2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole , and then in the process of generating oxaflutole according to the present invention, 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methylsulfonyl) ) phenyl]-4,5-dihydroisoxazole is monitored, thereby realizing the purpose of detecting and monitoring the synthesis of oxaflutole, which has a beneficial effect on the income of oxaflutole.

The present invention will be described in further detail below with reference to specific embodiments.

Description of drawings

Fig. 1 is 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methylsulfonyl)phenyl synthesized in Example 1-7 of the present invention ]-4,5-dihydroisoxazole LCMS chart;

Figure 2 is 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methylsulfonyl)phenyl] synthesized in Inventive Example 1-7 -1HNMR of 4,5 ^- dihydroisoxazole;

Figure 3 is the ¹ HNMR chart of 1-methyl-5-hydroxypyrazole in Examples 1-7 of the present invention;

Figure 4 is a ¹ HNMR chart of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole in Example 1-7 of the present invention;

Fig. 5 is the ¹ HNMR chart of 2,3-dimethylphenylthiomethane in Examples 1-7 of the present invention

Fig. 6 is the ¹ HNMR chart of 2,3-dimethyl-4-methylsulfonyl bromobenzene in Examples 1-7 of the present invention;

Fig. 7 is the ¹ HNMR chart of 3-bromo-2-methyl-6-methylsulfonylbenzaldehyde oxime in Example 1-7 of the present invention;

Figure 8a is 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxoxane azole liquid phase diagram;

Fig. 8b is the liquid phase diagram of oxaflutole standard product;

Figure 8c is a liquid phase diagram of oxaflutole in production.

Detailed ways

Example 3-[2-Methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole method of synthesis

This embodiment includes the following steps performed in sequence:

1) Preparation of raw materials, including preparation of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole and 1-methyl-5-hydroxypyridine azole, wherein the preparation method of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole is: using 2,3-dimethyl Aniline was used as the starting material, and 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4 was synthesized through methyl sulfide, bromination, oxidation, oxime formation, and chlorination ring closure, 5-dihydroisoxazole, the specific synthetic route is shown in route 1.

route 1

The route 1 includes the synthesis of 2,3-dimethylphenylthiomethane, the synthesis of 2,3-dimethyl-4-methylthiobromobenzene, the synthesis of 2,3-dimethyl-4- Synthesis of methylsulfonyl bromobenzene, 3-bromo-2-methyl-6-methylsulfonylbenzaldehyde oxime, 3-[3-bromo-2-methyl-6-(methylsulfonyl) For the synthesis of phenyl]-4,5-dihydroisoxazole, the synthesis of the above five substances will be described in this example.

A) Synthesis of 2,3-dimethylphenylthiomethane: add 500g of dimethyldisulfide, 100g of 2,3-dimethylaniline, and 52.55g of copper powder to a 1000 mL flask, raise the temperature to 50°C, and put it at 50°C. 135g of tert-butyl nitrite was added dropwise within 3 hours, and the lye solution absorbed the tail gas. After dripping, the reaction was continued at 50°C for one hour. After the reaction was completed, the copper powder was filtered, the sodium bicarbonate solution was used to wash the filtrate, and the dimethyl disulfide and the product 2,3-dimethylphenylthiomethane were separated by distillation under reduced pressure. The ¹ HNMR chart of the synthesized substance is shown in FIG. 5 .

B) Synthesis of 2,3-dimethyl-4-methylthiobromobenzene: at room temperature, add 109 g of 2,3-dimethylphenylthiomethane and 400 mL of acetic acid to a 1000 mL four-necked flask. Under the protection of N ₂ , a mixture of 114 g of liquid bromine and 100 mL of acetic acid was added dropwise, and the lye solution absorbed the waste gas, and the reaction was continued for 1 hour after the drop was completed. After the reaction is completed, filter the solid, add sodium acetate to the filtrate and stir, evaporate the acetic acid, add dichloromethane and water to stir, and concentrate the dichloro phase to obtain 2,3-dimethyl-4-methylbromothiobenzene.

C) Synthesis of 2,3-dimethyl-4-methylsulfonyl bromobenzene: To 182 g of 2,3-dimethyl-4-methylthiobromobenzene and 5.24 g of hydrated tungstic acid at 100 °C 266 g (30%) aqueous hydrogen peroxide solution was added dropwise to 600 mL of sodium acetic acid solution, the dropwise addition was completed, and the reaction was continued at this temperature for 1 hour. The reaction solution was cooled to 70°C, water was added to the reaction solution to separate out the product, filtered and dried to obtain 2,3-dimethyl-4-methylsulfonyl bromobenzene. The ¹ HNMR chart of the synthesized substance is shown in FIG. 6 .

D) Synthesis of 3-bromo-2-methyl-6-methylsulfonylbenzaldehyde oxime: 276 g of sodium methoxide was dissolved in 0.4 L of DMF, and 400 g of 2, A solution of 3-dimethyl-4-methylsulfonyl bromobenzene and 216.4 g of butyl nitrite in 0.8 L of DMF was then added with 100 g of sodium methoxide, and the reaction mixture was stirred for a total of 5.5 hours.

The mixture was poured into 4L ice water and 0.4L acetic acid and extracted with a total of 4L methyl tertiary ether, the organic phase was washed with sodium bicarbonate solution, and the organic phase was concentrated to give 3-bromo-2-methyl-6-methylsulfonyl Benzaldehyde oxime. The ¹ HNMR chart of the synthesized substance is shown in FIG. 7 .

E) Synthesis of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole: To 50 g of 3-bromo-2 at 60 °C - A small amount of N-chlorosuccinimide was added to a solution of methyl-6-methylsulfonylbenzaldehyde oxime in 200 mL of DMF. Once the reaction was started, 23.3 g of N-chlorosuccinimide in total was metered in at 40°C to 50°C. The reaction was stirred for an additional 30 minutes until the reaction was complete, the reaction mixture was poured into ice water, and the solid was filtered and washed twice with water. The solid was used directly in the next reaction.

The solid was dissolved in 250 mL of dichloromethane, replaced by ethylene gas, and ethylene gas was continuously introduced, and 20.3 g of triethylamine was added dropwise at the same time, and the reaction was carried out at room temperature for 72 hours under continuous introduction of ethylene. After the reaction is completed, wash with water and evaporate the solvent to obtain 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole. The ¹ HNMR chart of the synthesized substance is shown in FIG. 4 .

The method for synthesizing 1-methyl-5-hydroxypyrazole in this example is as follows: in an ice-water bath, add 170 g of methanol to a 1000 mL four-necked flask. At the same time, 116 g of methyl 3-methoxyacrylate and 262.8 g (35%) of methylhydrazine aqueous solution were added dropwise to the flask. After the dropwise addition was completed, the reaction was continued for 2 hours. After the reaction was completed, methanol, water and methylhydrazine were distilled off under reduced pressure. The product 1-methyl-5-hydroxypyrazole is obtained. The specific synthetic route is shown in Route 2. The ¹ HNMR chart of the synthesized substance is shown in FIG. 3 .

route 2

2) Condensation reaction

The prepared 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole was mixed with 1-methyl-5-hydroxypyrazole in basic Condensation reaction occurs under the conditions, and finally 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4 is prepared, 5-Dihydroisoxazole.

This step specifically includes:

①Add 200mL of solvent A to a 500mL flask, DMF was used as solvent A in this example, and then 14.9g of 3-(3-bromo-2-methyl-6-methylsulfonylphenyl)-4,5- Dihydroisoxazole and 16.18 g of potassium carbonate were used to obtain solution B, and the temperature was gradually raised to 140° C. under stirring.

2. 4.6g of 1-methyl-5-hydroxypyrazole is dissolved by 50mL of solvent A, and DFM is used to dissolve in the present embodiment, and then all is added dropwise to the solution B of the flask, after the dropwise addition, continue to heat up in step 1. At the following temperature (ie, at 140 °C), the reaction was completed to obtain solution C.

3. After the reaction is completed, the solution C is cooled to room temperature, poured into cold water, and then extracted with ethyl acetate, washed with water, dried and concentrated to obtain 3-[2-methyl-3-(1-methyl-1H- Pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole solid.

of the above-mentioned 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole The specific synthetic route is shown in route 3. The LCMS chart of the synthesized material is shown in FIG. 1 ; the ¹ HNMR chart of the synthesized material is shown in FIG. 2 .

line 3

Example 2-7 3-[2-Methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydro The synthetic method of isoxazole

Embodiments 2-7 are respectively a kind of 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methylsulfonyl)phenyl]-4, The synthetic method of 5-dihydroisoxazole, its synthetic method and synthetic route are basically the same as the synthetic method of embodiment 1, and the difference is that in each step 2., the solvent type used and the variation of each material parameter added, see the table specifically 1

Table 1

Example 8 3-[2-Methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxoxane Application of azoles

This implementation is 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxyl)-6-(methyl) prepared by any one of the synthetic methods in Examples 1-7 Use of sulfonyl)phenyl]-4,5-dihydroisoxazole, namely 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)- 6-(Methylsulfonyl)phenyl]-4,5-dihydroisoxazole can be used as a standard reference to detect the presence of 3-[2-methyl-3-(1-methyl-1H) of oxaflutole -Pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole and how much it is in.

In addition, in the process of synthesizing oxaflutole by the above method, it can be used as a standard to detect and monitor the generation of this impurity, which is of great significance to the improvement of reaction conditions. As shown in Figure 8a to Figure 8c, by comparing the liquid phase diagrams of the oxaflutole standard and the in-production oxaflutole, and 3-[2-methyl-3-(1-methyl-1H-pyridoxine) The liquid phase diagram of oxazole-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole, it can be seen that the produced oxaflutole product contains 3-[2-methyl yl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole impurity, further illustrating the 3-[ Application of 2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole as a standard value.

Claims (7)

1. a synthetic method of oxaflutole impurity, is characterized in that: described impurity is 3-[2-methyl-3-(1-methyl-1H-pyrazole-5-oxyl)-6- (Methylsulfonyl)phenyl]-4,5-dihydroisoxazole, the synthesis method thereof comprises the following steps which are carried out in sequence: 1) Preparation of raw materials, including preparation of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole and 1-methyl-5-hydroxypyridine azole, wherein the preparation method of the 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole is to use 2,3-dimethyl Aniline was used as the starting material, and 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4 was synthesized through methyl sulfide, bromination, oxidation, oxime formation, and chlorination ring closure, 5-dihydroisoxazole; The synthetic method of the 1-methyl-5-hydroxypyrazole is to synthesize 1-methyl-5-hydroxypyrazole by reacting methyl 3-methoxyacrylate and methylhydrazine; 2) Condensation reaction The prepared 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole was mixed with 1-methyl-5-hydroxypyrazole in basic Condensation reaction occurs under the conditions, and finally 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4 is prepared, 5-Dihydroisoxazole. 2. the synthetic method of oxaflutole impurity according to claim 1, is characterized in that: The 3-[2-methyl-3-(1-methyl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole The synthetic circuit is: . 3. the synthetic method of the oxaflutole impurity according to claim 1 and 2 is characterized in that described step 2) is carried out according to the following step sequence: ①Add catalyst base and 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole to solvent A and dissolve to obtain solution B. The solution B is heated to 80～150 ℃; ② Dissolve 1-methyl-5-hydroxypyrazole in solvent A, add dropwise to the reaction flask, mix with solution B, and complete the reaction at the temperature of step ①, and obtain reaction solution C after the reaction is completed; 3. The reaction solution C was lowered to room temperature and poured into ice water, extracted with ethyl acetate or dichloromethane, the organic phase was washed with water, and then concentrated to obtain 3-[2-methyl-3-(1-methyl-1H -Pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole. 4. the synthetic method of oxaflutole impurity according to claim 3, is characterized in that: the catalyst base in described step 1. is any one in sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide, The molar equivalent ratio of the amount of the base to the amount of 3-[3-bromo-2-methyl-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole is 0.5 to 5:1 . 5. the synthetic method of oxaflutole impurity according to claim 3, is characterized in that: described step 1. and step 2. used solvent A is any one in DMF, DMAC, NMP. 6. the synthetic method of oxaflutole impurity according to claim 3, is characterized in that: used 1-methyl-5-hydroxypyrazole and 3-[3-bromo-2-methyl-6-(methyl) The molar equivalent ratio of the amount of phenylsulfonyl)-phenyl]-4,5-dihydroisoxazole is 1-1.5:1. 7. a 3-[2-methyl-3-(1-methyl-1H-pyrazole- The application of 5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole, characterized in that: the 3-[2-methyl-3-(1-methyl) yl-1H-pyrazol-5-oxy)-6-(methylsulfonyl)phenyl]-4,5-dihydroisoxazole was used as a standard to detect and monitor the synthesis of oxaflutole .