2-methyl-3-(trifluoromethyl)aniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Similarly, the 3-amino-4-chloro-2-methylthiomethylbenzotrifluoride may be replaced with equivalent quantities of 3-amino-4-bromo-2-methylthiomethylbenzotrifluoride, 3-amino-4-iodo-2-methylthiomethylbenzotrifluoride, 3-amino-4-methylthio-2-methylthiomethylbenzotrifluoride, 3-amino-4-ethylthio-2-methylthiobenzotrifluoride, 3-amino-4-n-propylthio-2-methylthiomethylbenzotrifluoride, 3-amino-4-n-butylthio-2-methylthiomethylbenzotrifluoride, 3-amino-4-heptylthio-2-methylthiomethylbenzotrifluoride, or 3-amino-4-octylthio-2-methylthiomethylbenzotrifluoride, and by following substantially the process of Example 2, step B, there is produced 3-amino-2-methylbenzotrifluoride.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 2 g. of 3-amino-4-chloro-2-methylthiomethylbenzotrifluoride in 50 ml. of 90% ethanol which is 1N in potassium hydroxide. Add 2 teaspoonsful of Raney nickel (W-2). Stir at 70° C. for 3 hours, cool and filter. Add 50 ml. of water and extract three times with hexane. Dry the combined organic extracts and evaporate to yield the title compound. Dissolve 2 g cool filter Add 50 ml of water and extract three times with hexane Dry the combined organic extracts evaporate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using 5-chlorosalicylic acid and 2-methyl-3-(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ) A mixture of 2-methyl-3-trifluoromethylaniline (368 g, 2.1 moles) and 2-chloronicotinic acid (158.0 g, 1.0 mole) in 400 ml of water is heated at 100° C. for 24 hours together with p-toluenesulfonic acid (15.0 g) monohydrate as the acid catalyst. Potassium hydroxide (ca. 145 g) in water (255 ml) is added and the pH is maintained above 11. After diluting the reaction mixture to 1.2 liters with water, the mixture is cooled to 50° C., adjusted to pH 11, treated with 7 g of a decolorizing charcoal and 15 g of a filter aid, and clarified by filtration. The flitrate is diluted with 750 ml of water and the pH is adjusted to 5.0 with concentrated sulfuric acid. Agitation of the suspension for 10 minutes and filtration gives crude, precipitated 2-[[2-methyl-3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic acid (flunixin) (83% yield). The compound can be further purified by crystallization in methanol and washing with water. the pH is maintained above 11 clarified by filtration The flitrate is diluted with 750 ml of water filtration gives crude

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20 mol of concentrated hydrochloric acid is added at 0°-5° C. to a suspension of 16.7 g of 2-methyl-3-trifluoromethylaniline (0.095 mol) in 50 ml mixture is then briefly warmed to 60°-80° C. until a clear solution has formed. The solution is cooled very rapidly to 0°-5° C. with vigorous stirring, 22.4 ml (0.286 mol) of acrylonitrile are added dropwise to the fine suspension at 0°-5° C. and a solution of 6.75 g of sodium nitrite in 10 ml of water is then rapidly added, and the mixture is kept at 5° C. for a further 5 minutes and stirred at 20° C for 1 hour. After cooling, 0.8 g of copper(II) oxide powder is added to the reaction mixture at 0°-10° C. in portions, a vigorous evolution of nitrogen gas occurring. After completion of the evolution of gas, the mixture is stirred for a further 2 hours at 0°-10° C., then for 15 hours at room temperature, dichloromethane is added, and the mixture is washed with water, dried over sodium sulphate and concentrated in vacuo. 21.2 g (90% of theory) of 2-chloro-3-(2-methyl-3-trifluoromethylphenyl)-propionitrile are obtained as a brown oil. M/e 247 (M+), 228, 212, 173 (100%) is then briefly warmed to 60°-80° C. until a clear solution has formed are added dropwise to the fine suspension at 0°-5° C. After cooling After completion of the evolution of gas, the mixture is stirred for a further 2 hours at 0°-10° C. for 15 hours at room temperature the mixture is washed with water dried over sodium sulphate concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-3-iodo-N-(2-methyl-3-(trifluoromethyl)phenyl)benzamide was synthesized from 2-methyl-3-(trifluromethyl)aniline and 4-chloro-3-iodobenzoyl chloride according to the procedure described in Example 183. 4-Chloro-3-iodo-N-(2-methyl-3-(trifluoromethyl)phenyl)benzamide was obtained as a white solid. MS (M−H+) 437.8; Calculated for C15H10ClF3INO: 439.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized according to the procedure described for the preparation of Example 231 using 6 (50 mg, 0.22 mmol) and 2-methyl-3-trifluoromethyl-phenylamine (0.03 mL, 0.33 mmol) to provide 237 (23 mg, 28% yield) as a brown solid. LC-MS (M+H=370, obsd.=370). The title compound was synthesized

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized according to the procedure described for the preparation of Example 231 using 6 (50 mg, 0.22 mmol) and 2-methyl-3-trifluoromethyl-phenylamine (0.03 mL, 0.33 mmol) to provide 237 (23 mg, 28% yield) as a brown solid. LC-MS (M+H=370, obsd.=370). The title compound was synthesized

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of chloral hydrate (6.08 g, 36.74 mmol) and anhydrous sodium sulfate (28.5 g, 200.4 mmol) in water (102 mL) add a mixture of hydroxylamine sulfate (28.5 g, 173.68 mmol), 2-methyl-3-trifluoromethyl-phenylamine (5.85 g, 33.4 mmol), concentrated hydrochloric acid (3.5 mL) in water (34 mL). Heat the mixture at 35° C. for 1 h, then heat up to 52° C. for 90 min and at 75° C. for 1 h. Cool the mixture to room temperature and filter the solid. Wash the solid with water and hexane. Dry the solid under vacuum to afford 2-hydroxyimino-N-(2-methyl-3-trifluoromethyl-phenyl)-acetamide: MS (ES+): 245 (M−H). Add the former crude in small portions at 60° C. to concentrated sulfuric acid (44 mL) and heat the mixture at 80° C. for 1 h. Cool to room temperature, pour into ice water (100 mL) and filter the precipitate. Wash the solid with cool water twice. Dry the solid to afford the title compound (3.54 g, 46% two steps). MS (ES−): 228 (M−H). heat up to 52° C. for 90 min and at 75° C. for 1 h Cool the mixture to room temperature filter the solid Wash the solid with water and hexane Dry the solid under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-3-iodo-N-(2-methyl-3-(trifluoromethyl)phenyl)benzamide was synthesized from 2-methyl-3-(trifluromethyl)aniline and 4-chloro-3-iodobenzoyl chloride according to the procedure dscribed in Example 183. 4-Chloro-3-iodo-N-(2-methyl-3-(trifluoromethyl)phenyl)benzamide was obtained as a white solid. MS (M−H+) 437.8; Calculated for C15H10ClF3INO: 439.