CN117720405A - Synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone - Google Patents
Synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone Download PDFInfo
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- CN117720405A CN117720405A CN202311540424.2A CN202311540424A CN117720405A CN 117720405 A CN117720405 A CN 117720405A CN 202311540424 A CN202311540424 A CN 202311540424A CN 117720405 A CN117720405 A CN 117720405A
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 title claims abstract description 13
- 238000001308 synthesis method Methods 0.000 title abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 30
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 20
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 16
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- 229940126062 Compound A Drugs 0.000 claims description 8
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000012074 organic phase Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 239000012300 argon atmosphere Substances 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 2
- DBTNVRCCIDISMV-UHFFFAOYSA-L lithium;magnesium;propane;dichloride Chemical compound [Li+].[Mg+2].[Cl-].[Cl-].C[CH-]C DBTNVRCCIDISMV-UHFFFAOYSA-L 0.000 claims description 2
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 claims description 2
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 claims description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 10
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- GCICAPWZNUIIDV-UHFFFAOYSA-N lithium magnesium Chemical compound [Li].[Mg] GCICAPWZNUIIDV-UHFFFAOYSA-N 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 4
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 10
- QRPRXRQFNNXPBA-UHFFFAOYSA-N 1-bromo-3-chloro-5-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(Cl)=CC(Br)=C1 QRPRXRQFNNXPBA-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000012535 impurity Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000077 insect repellent Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 241000238876 Acari Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940058878 nexgard Drugs 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone, belonging to the technical field of fine chemicals. The method comprises the following steps: the method has the technical scheme that compared with the prior art, the method can fully convert raw materials into the magnesium-lithium reagent, the activity of the magnesium-lithium reagent is lower than that of the phenyl-lithium reagent, and the magnesium-lithium reagent and ethyl trifluoroacetate can obtain a product with stable environment at a proper temperature.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone.
Background
The new-generation oral in vitro insect repellent Nishi (NexGard) (common name: affrana chewing tablet) for dogs is the first oral insect repellent for dogs for killing two parasites, namely ticks and fleas.
1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone is a key intermediate for synthesizing aforana, a product synthesis method disclosed in patent WO 2011054436A 2 adopts 3-chloro-5-trifluoromethyl bromobenzene as a raw material, and is synthesized by preparing a format reagent through magnesium metal, the reaction yield is 78%, but dechlorinated impurities exist in the product, so that the product with high purity is difficult to obtain, great difficulty is brought to purification, the aforana API can be always derived when the aforana API is prepared later, and the aforana API meeting the quality standard cannot be obtained.
The inventors of the present application have found that there is room for further improvement in the purity of the product, yield, reaction conditions, etc. by reproducing the process of WO 2011054436.
Disclosure of Invention
Aiming at the technical problems of low yield, more impurities, severe reaction and low product purity existing in the 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone process in the prior art, the invention takes 3-chloro-5-trifluoromethyl bromobenzene as a raw material and carries out substitution reaction in the presence of a catalyst and alkali to obtain the 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone.
In order to solve the technical problems, the invention adopts the following technical scheme:
the invention provides a synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone, which comprises the following steps: reacting the compound A with a compound B in the presence of a catalyst and alkali to obtain a compound C, namely 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone; the reaction process is as follows:
wherein the alkali is at least one selected from n-butyllithium, tert-butyllithium and methyllithium. Preferably, the base is n-butyllithium.
The catalyst is at least one selected from isopropyl magnesium chloride, methyl magnesium chloride, isopropyl magnesium chloride lithium chloride and ethyl magnesium chloride. Preferably, the catalyst is isopropyl magnesium chloride, which is favorable for reaction.
The molar ratio of the compound A to the compound B is 1:1 to 1:2. Preferably, the molar ratio of compound a to compound B is from 1:1.2 to 1:2. More preferably, the molar ratio of compound A to compound B is 1:1.5, 1:1.8, 1:2.
In some embodiments, the reaction temperature is from-80 ℃ to 10 ℃. Preferably, the reaction temperature is from-70℃to-10 ℃. Most preferably, the reaction temperature is-60 ℃.
In some embodiments, the above reaction is performed under an inert atmosphere selected from at least one of an argon atmosphere, a nitrogen atmosphere, and a helium atmosphere.
In some embodiments, the reaction solvent of the above reaction is selected from at least one of tetrahydrofuran, 2-methyltetrahydrofuran, toluene. Preferably, the reaction solvent is tetrahydrofuran.
In some embodiments, the molar ratio of the catalyst to compound B is from 0.4:1 to 0.6:1. Preferably, the molar ratio of catalyst to compound B is from 0.5:1 to 0.6:1. More preferably, the molar ratio of catalyst to compound B is 0.52:1.
In some embodiments, the molar ratio of base to compound B is from 1:1 to 1:2. Preferably, the molar ratio of base to compound B is from 1.2:1 to 1.8:1. More preferably, the molar ratio of base to compound B is 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7.
In some embodiments, after the reaction is complete, further post-treatments may be performed, including: adding water and HCl to adjust pH to less than 5, separating, washing, drying, filtering, concentrating, and distilling under reduced pressure to obtain compound C. Preferably, after the reaction is completed, further post-treatment may be performed, including: adding water and HCl to adjust pH to less than 5, separating, washing the upper organic phase with water and saturated saline, drying with anhydrous sodium sulfate, filtering, concentrating to obtain crude product, and distilling under reduced pressure to obtain compound C.
In some embodiments, a method of synthesizing 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone comprises: the compound A is replaced by nitrogen in tetrahydrofuran at the temperature of between 70 ℃ below zero and 50 ℃ below zero, isopropyl magnesium chloride, n-butyl lithium and compound B are added, and the temperature is gradually increased to 20 ℃ below zero to react completely; adding water and HCl to regulate pH to less than 5, separating, washing the upper organic phase, drying, filtering, concentrating to obtain coarse product, and vacuum distilling to obtain compound C.
In the present invention, in order to improve the yield and product purity of the reaction, the reaction requires strict control of the moisture content below 2000ppm, including but not limited to: the containers used need to be dried and the purchased solvents need to be redistilled or dried to remove water to control the moisture content.
In the present invention, in order to increase the yield and product purity of the reaction, the reaction requires strict control of the reaction temperature, including but not limited to: the reaction temperature is controlled at-70 ℃ to-50 ℃ before the last reaction substrate such as compound B or compound A is added, and the temperature is slowly raised after the last reaction substrate such as compound B or compound A is added, so that the reaction is carried out at-20 ℃.
Compared with the prior art, the invention has the following beneficial technical effects:
compared with the prior art, the technical scheme of the invention adopts a synthesis method, and has the innovation point that 3-chloro-5-trifluoromethyl bromobenzene is used as a starting material, the starting material can be completely converted into a magnesium-lithium reagent in the presence of isopropyl magnesium chloride and butyl lithium, the activity of the magnesium-lithium reagent is lower than that of a phenyl-lithium reagent, and a product with stable environment can be obtained by using ethyl trifluoroacetate at a proper temperature. Single reaction and less side reaction of reaction liquid. Compared with the method for preparing the format reagent by using magnesium to prepare the 3-chloro-5-trifluoromethyl bromobenzene in the document WO2011054436, the method has the characteristics of advantages, low activity, higher temperature required for reaction with ethyl trifluoroacetate, larger debrominated impurities and coupling impurities, poor control of reaction, difficult purification, low yield and the like.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
In the present invention, the expressions "compound 1" and "compound represented by formula 1" and "formula 1" mean the same compound.
In the present invention, optional means that the post-treatment may or may not be performed, e.g., optional post-treatment means that the post-treatment may or may not be performed.
Detailed Description
In order to better understand the technical solution of the present invention, the following further discloses some non-limiting examples, which are further described in detail.
The reagents used in the present invention are all commercially available or can be prepared by the methods described herein.
In the present invention, min represents minutes; h represents hours; g represents gram; ml represents milliliters.
In the present invention, GC means gas chromatography.
In the present invention, the reaction completion means that the reaction raw material remains 1% or less.
Example 1
Adding 259.45g of tetrahydrofuran 1295mL and 3-chloro-5-trifluoromethyl bromobenzene into a dried 3L reaction bottle, cooling to-70 ℃, replacing with nitrogen atmosphere, adding 260mL of isopropyl magnesium chloride, stirring for 15min, then dropwise adding 416mL of n-butyl lithium, maintaining the temperature of the system at about-50 ℃ to-60 ℃ for 0.5 h, then dropwise adding 270g of ethyl trifluoroacetate, maintaining the temperature at-60 ℃ to-50 ℃, keeping the temperature for 1 h, gradually heating to react to-20 ℃, and reacting for 8h. GC detection of less than 0.2% starting material was considered the reaction reached the end point. 250ml of water and 600ml of 2M HCL are added into the system to adjust the pH to be less than 5, the mixture is separated, the upper organic phase is washed by water and saturated saline water, dried by anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was distilled under reduced pressure to give compound C,257.6g, yield: 93%, purity 99.9%.
Example 2
The effect of solvents, bases, and catalysts on the purity and yield of compound C in the reaction was examined according to the method in example 1.
TABLE 1 influence of solvent, base, catalyst on purity and yield of Compound C
As can be seen from Table 1, through screening, tetrahydrofuran is selected as a solvent, n-butyllithium is selected as a base, a catalyst is isopropyl magnesium chloride, and the purity of a compound C product can reach more than 99%, and the yield can reach more than 93%.
Example 4
According to the method in example 1, tetrahydrofuran was fixed as a solvent, n-butyllithium as a base, isopropyl magnesium chloride as a catalyst, and other conditions were not changed, and the reaction temperature in the reaction, the molar ratio of compound a to compound B, the molar ratio of catalyst to compound B, and the influence of the molar ratio of base to compound B on the purity and yield of compound C were examined.
TABLE 2 influence of variation of process parameters on purity and yield of Compound C
As can be seen from table 2, the ratio of compound a to compound B is 1:1.5, the catalyst is selected to take the cost into account at a temperature ranging from-70 ℃ to 50 ℃): the ratio of compound B is 0.5:1 and base: when the ratio of the compound B is 1:1.5, the progress of the reaction is facilitated.
Comparative example 1
Compound C was prepared according to the method in WO2011054436 to give compound C in a yield of 78% and a purity of 93% by liquid phase detection, 215 g.
Comparative example 2
Adding 259.45g of tetrahydrofuran 1295mL and 3-chloro-5-trifluoromethyl bromobenzene into a dried 3L reaction bottle, cooling to-50 ℃, replacing with nitrogen atmosphere, adding 260mL of isopropyl magnesium chloride, stirring for 15min, then dropwise adding 416mL of n-butyl lithium, maintaining the temperature of the system at about-50 ℃ to-30 ℃ for 0.5 h, then dropwise adding 270g of ethyl trifluoroacetate, maintaining the temperature at-50 ℃ to-30 ℃, keeping the temperature for 1 h, gradually heating to react to-20 ℃, and reacting for 8h. GC detection of less than 0.2% starting material was considered the reaction reached the end point. 250ml of water and 600ml of 2M HCl are added into the system to adjust the pH to be less than 5, the mixture is separated, the upper organic phase is washed by water and saturated saline, dried by anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was distilled under reduced pressure to give compound C,171.7g, yield: 60% and 87% purity.
While the methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations and combinations of the methods and applications described herein can be made and applied within the spirit and scope of the invention. Those skilled in the art can, with the benefit of this disclosure, suitably modify the process parameters to achieve this. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included within the present invention.
Claims (10)
1. A method for synthesizing 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone, which comprises the following steps: reacting the compound A with a compound B in the presence of a catalyst and alkali to obtain a compound C, namely 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone;
wherein the alkali is at least one selected from n-butyllithium, tert-butyllithium and methyllithium; the catalyst is at least one selected from isopropyl magnesium chloride, methyl magnesium chloride, isopropyl magnesium chloride lithium chloride and ethyl magnesium chloride.
2. The method according to claim 1, wherein the molar ratio of compound a to compound B is from 1:1 to 1:2.
3. The process of claim 1, wherein the reaction temperature is from-80 ℃ to 10 ℃.
4. The method according to claim 1, wherein the reaction is carried out under an inert atmosphere selected from at least one of an argon atmosphere, a nitrogen atmosphere, and a helium atmosphere.
5. The method according to claim 1, wherein the reaction solvent is at least one selected from the group consisting of tetrahydrofuran, 2-methyltetrahydrofuran, and toluene.
6. The process according to claim 1, wherein the molar ratio of catalyst to compound B is from 0.4:1 to 0.6:1.
7. The process according to claim 1, wherein the molar ratio of base to compound B is from 1:1 to 1:2.
8. The method according to claim 1, wherein after the reaction is completed, further post-treatment is performed, the post-treatment comprising: adding water and HCl to adjust pH to less than 5, separating, washing, drying, filtering, concentrating, and distilling under reduced pressure to obtain compound C.
9. A method for synthesizing 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoroethanone, which comprises the following steps: the compound A is replaced by nitrogen in tetrahydrofuran at the temperature of between 70 ℃ below zero and 50 ℃ below zero, isopropyl magnesium chloride, n-butyl lithium and compound B are added, and the temperature is gradually increased to 20 ℃ below zero to react completely; adding water and HCl to regulate pH to less than 5, separating, washing the upper organic phase, drying, filtering, concentrating to obtain coarse product, and vacuum distilling to obtain compound C.
10. The method according to any one of claims 1 to 9, wherein the reaction requires strict control of the moisture content, said control of the moisture content being below 2000 ppm.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311540424.2A CN117720405A (en) | 2023-11-20 | 2023-11-20 | Synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311540424.2A CN117720405A (en) | 2023-11-20 | 2023-11-20 | Synthesis method of 1- [ 3-chloro-5- (trifluoromethyl) phenyl ] -2, 2-trifluoro-ethanone |
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