Tofenacin Hydrochloride

The compound 2-amino-2, 6 -propionoxylidide was synthesized by saturating with gaseous ammonia at room temperature a suspension of 50 g (0.195 mol) of 2-bromo-2, 6 -propion-oxylidide in a mixture of 500 ml of 95% alcohol and 400 ml of concentrated aqueous ammonia. The saturation was carried out under mechanical stirring. After 25 hours the mixture was resaturated with ammonia gas. The stirring at room temperature was continued for a total period of 116 hours, and a sample was taken at that time. Gas chromatographic analysis indicated that about 95% of the bromo compound had been converted to the desired product. 

The solvents were evaporated in vacuo, and the residue was taken up in 80 ml of 3M hydrochloric acid. After addition of 220 ml of water, the insoluble material was filtered off, washed with 100 ml of water and then dried. The insoluble material weighed 9.5 g and was mainly unreacted bromo compound. The filtrate was reacted with 50 ml of 7 M NaOH, extracted three times with methylene chloride (50 m -t 2 x 25 ml portions), dried over potassium carbonate, and then evaporated. The yield of residue was 26.8 g which corresponds to 71.4% of the theoretical yield. This residue was a colorless solidifying oil and was dissolved in 200 ml chloroform. Hydrogen chloride was bubbled in until a sample of the solution tested acidic to wet pH indicator paper. A precipitate was obtained and recovered by filtration. The precipitate was washed with chloroform and dried. The melting point was determined to be from 246 Cto247.5°C. 

Chemical Name N-methyl-2-[(2-methylphenyl)phenylmethoxy] ethanamine hydrochloride 

Common Name N-demethylorphenadrine hydrochloride N-methyl-2[o -(2-tolybenzyl)oxy]-ethylamine hydrochloride 

A mixture of 39.5 grams of 2-methylbenzhydrol, 200 ml of beta-chloroethanol and 10 ml of concentrated hydrochloric acid is boiled under reflux for 4 hours. After cooling, the reaction mixture is poured into water and extracted with petroleum ether (boiling range 40° to 60°C). The layers are separated and the ethereal solution dried with sodium sulfate. It is then filtered. The filtrate is concentrated by evaporation of the solvent. The residue is distilled under reduced pressure to give 51.0 grams (yield 98%) of beta-chloroethyl-2-methylbenzhydryl ether, boiling at 156° to 158°C/2.5 mm. 

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Infra-red Spectrum. Principal peaks at wavenumbers 1102, 704, 757, 1117, 1042, 917 (tofenacin hydrochloride, KBr disk). 

Tocainide hydrochloride, 1028 Toclase, 431 Tocomine, 329 Tocopherol acetate, 329 Tocopheryl acetate, 329 Tofenacin, 1028 (metabolite), 833 Tofenacin hydrochloride, 1028 Tofranil, 679 Tofranil-PM, 679 Togiren, 589 Toilax, 397 Tokols, 329 Tolanase, 1029 Tolazamide, 1029 Tolazoline, 1029 Tolazoline hydrochloride, 1029 Tolbutamide, 1030 Tolbutamide sodium, 1030 Tolbutone, 1030 Tolectin, 1032 Tolerance to drugs, 298 Tolerzide, 663 Tolerzide, 971 Tolfenamic acid, 1031 Tolglybutamide, 1030... 

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