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With potassium fluoride; nitrobenzene In sulfolane at 200 - 220℃; for 17 h;
Example 3; Preparation method of 3,4,5-trifluorobenzotrifluoride; 860 g of dry sulpholane and 524 g of dry KF were initially charged with exclusion of moisture in an autoclave, and 500 g of 3,4,5-trichlorobenzotrifluoride, 5 g of nitrobenzene and 25 g of CNC catalyst were added. The vessel was sealed and the mixture subsequently heated to 200° C. for 5 h and then to 220° C. for a further 12 h. During the reaction, a maximum total pressure of 9 bar arose. The mixture was then cooled to 20° C. and decompressed into a cooled receiver. The product was distilled off at standard pressure. After redistillation of the crude product, 300 g of 3,4,5-trifluorobenzotrifluoride (75percent of theory) were obtained as a colourless liquid.
Preparation 21 (2,6-Difluoro-4-trifluoromethyl-phenyl)-hydrazine A mixture of <strong>[80172-04-9]1,2,3-trifluoro-5-(trifluoromethyl)benzene</strong> (300 g, 1.5 mmol) and hydrazine monohydrate (300 g, 6.0 mmol) in ethanol (1200 ml) was heated at reflux overnight. The reaction mixture was concentrated in vacuo and the residue was re-crystallized from 2-propanol to give Preparation 21 (194 g). MS (ES): M/Z [MH+] 213.2; expected mass for C7H5F5N2+H is 213.1 1H-NMR (CDCl3): 3.81-4.08 (2H), 5.23-5.41 (1H), 7.03-7.14 (2H)
With potassium fluoride; nitrobenzene;1,3-dimethyl-2-(N',N',N",N"-tetramethylguanidino)-4,5-dihydro-3H-imidazolium chloride; In sulfolane; at 200 - 220℃; under 6750.68 Torr; for 17h;
Example 3; Preparation method of 3,4,5-trifluorobenzotrifluoride; 860 g of dry sulpholane and 524 g of dry KF were initially charged with exclusion of moisture in an autoclave, and 500 g of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong>, 5 g of nitrobenzene and 25 g of CNC catalyst were added. The vessel was sealed and the mixture subsequently heated to 200 C. for 5 h and then to 220 C. for a further 12 h. During the reaction, a maximum total pressure of 9 bar arose. The mixture was then cooled to 20 C. and decompressed into a cooled receiver. The product was distilled off at standard pressure. After redistillation of the crude product, 300 g of 3,4,5-trifluorobenzotrifluoride (75% of theory) were obtained as a colourless liquid.
1-Cyclopropyl-7,8-difluoro-5-trifluoromethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid STR88 a) 2,3,4-Trifluoro-6-trifluoromethylbenzoic acid The title compound is obtained when <strong>[80172-04-9]1,2,3-trifluoro-5-trifluoromethylbenzene</strong> is reacted analogously to Example Ya. Melting point:83-84 C.
Example IV-4 In a stainless steel autoclave, 500 g of <strong>[80172-04-9]3,4,5-trifluoro-benzotrifluoride</strong> are introduced, 2,000 ml of tetrahydrofuran are added, and 150 g of liquid ammonia are forced in. The autoclave is heated to 120 to 130 C. for 5 hours with stirring, then cooled, and the pressure is released at 20 C. In addition to the solvent and the starting material, 272 g of 3,5-difluoro-4-amino-benzotrifluoride of a boiling point of 58 to 60 C. at 16 mbar are obtained by distillation.
With ammonia; In tetrahydrofuran;
EXAMPLE 3 500 g of <strong>[80172-04-9]3,4,5-trifluoro-benzotrifluoride</strong> were initially introduced into a stainless steel autoclave, 2000 ml of tetrahydrofuran were added and it was pressurized using 150 g of liquid ammonia. The autoclave was heated at 120 to 130 C. for 5 hours with stirring, then cooled and the pressure released at 20 C. In addition to the solvent and starting material, 272 g of 3,5-difluoro-4-aminobenzotrifluoride having a boiling point of 58 to 60 C. at 16 mbar were obtained by distillation.
1-(2,6-difluoro-4-trifluoromethylphenyl)-4-trifluoromethyl-2-pyridone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In N-methyl-acetamide;
EXAMPLE 1 This Example illustrates the preparation of 1-(2,6-difluoro-4-trifluoromethylphenyl)-4-trifluoromethyl -2-pyridone (Compound No. 20, Table I). A well stirred mixture of 4-trifluoromethyl-2-pyridone (1.5 g, 9.2 mmol), <strong>[80172-04-9]3,4,5-trifluorobenzo trifluoride</strong> (9.2 g, 46 mmol) and potassium carbonate (6.3 g, 46 mmol) in dimethylformamide (40 ml) was heated at 100 C. under nitrogen for 5 hours. The reaction mixture was poured into water (100 ml), acidified with dilute hydrochloric acid and extracted with chloroform (2*75 ml). The combined organic layers were washed with water (3*100 ml) dried over magnesium sulphate and evaporated in vacuo. The resulting oil was purified by column chromatography on silica with 2:1 petrol - diethyl ether eluent followed by crystalisation from a petrol - diethyl ether mixture to give the required compound as a white solid (680 mg, mp 136-137 C.);delta(d6 -acetone), 8.10 (1H,m); 7.9 (2H,d); 7.1 (1H,m); 6.76 (1H,dd).
3-carbomethoxymethyl-5-hydroxybenzoxazolone[ No CAS ]
3-carbomethoxymethyl-5-(2,6-difluoro-4-trifluoromethylphenoxy)-benzoxazolone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; dimethyl sulfoxide; In water;
EXAMPLE V Preparation of: 3-carbomethoxymethyl-5-(2,6-difluoro-4-trifluoromethylphenoxy) benzoxazolone A mixture of 1.33 grams (0.006 mole) of 3-carbomethoxymethyl-5-hydroxybenzoxazolone, 1.32 grams (0.0066 mole) of <strong>[80172-04-9]3,4,5-trifluorobenzotrifluoride</strong>, 1.24 grams (0.009 mole) of potassium carbonate and 20 milliliters of dimethyl sulfoxide was stirred at room temperature until HPLC analysis indicated substantially complete conversion of starting materials. The reaction mixture was then poured into 100 milliliters of water and extracted twice with methylene chloride. The organic phase was extracted once with water and evaporated at reduced pressure. The aqueous phase was extracted twice with diethyl ether and the resultant organic phase was extracted twice with water then dried over anhydrous magnesium sulfate and evaporated at reduced pressure. The combined evaporated residues afforded 1.84 grams of an oily material confirmed by MS analysis as the desired product.
2-nitro-5(2,6-difluoro-4-trifluoromethyl)benzoic acid[ No CAS ]
[ 80172-07-2 ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In N-methyl-acetamide;
EXAMPLE 6 This Example illustrates the preparation of 3-(2,6-difluoro-4-trifluoromethylphenoxy)benzoic acid by the process of claim 1. A solution of 3-hydroxybenzoic acid (5.5 g) and <strong>[80172-04-9]3,4,5-trifluorobenzotrifluoride</strong> (8.3 g) in dimethylformamide (50 ml) was stirred with anhydrous potassium carbonate (14 g) for 4 hours at 100. The mixture was then diluted with water (200 ml) and acidified. The mixture was extracted with ether and the ether extract dried and evaporated to give the required compound (7.2 g) with a melting point of 140-146. Nitration of this product gave 2-nitro-5(2,6-difluoro-4-trifluoromethyl)benzoic acid.
Example 18 Sodium hydride (17 mg) was added to a solution of 3-chloro-4-[5-[1-hydroxy-1-methylethyl]-4-methyl-4H-1,2,4-triazol-3-yl}benzonitrile(100 mg) in DMF (1 ml) under ice cooling, followed by stirring at the same temperature for 10 minutes, and 3,4,5-trifluorobenzenotrifluoride (87 mg) was added thereto, followed by stirring in an ice bath for 3 hours. Water was added to the reaction mixture to cease the reaction followed by extraction with ethyl acetate. The organic layer was washed with water twice, then washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:chloroform=100:0 to 100:2). The residue was powdered in diethylether, collected by filtration and washed with diethylether. The resulting powder was suspended in ethanol, an aqueous hydrogen peroxide solution (86 mul) and a 1M aqueous sodium hydroxide solution (0.4 ml) were sequentially added thereto under ice cooling, followed by stirring at room temperature for 2 hours. Water and ethyl acetate were added thereto with ice-cooling to perform separation operation. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and then by thin layer chromatography, powdered in diethylether and then collected by filtration to obtain 3-chloro-4-(5-{1-[2,6-difluoro-4-(trifluoromethyl)phenoxy]-1-methylethyl}-4-methyl-4H-1,2,4-triazol-3-yl}benzamide (45.7 mg), as a white powder.