2,2,2-trifluoro-N-[2-(4-methoxyphenyl)ethyl]acetamide

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 32.2 ml (0.23 mol) of trifluoroacetic acid were added dropwise to a solution of 22.3 ml (0.15 mol) of 2-(4-methoxyphenyl)ethylamine and 24.7 ml (0.23 mol) of pyridine in 125 ml of absolute THF cooled to 5° C., and the resulting solution was stirred at RT for 3 h. The reaction solution was then poured onto 750 ml of ice, and the deposited precipitate was filtered off with suction and dried at 40° C. in a high vacuum. 36.3 g of the title compound were obtained as a beige solid. the deposited precipitate was filtered off with suction dried at 40° C. in a high vacuum

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

Procedure: The product from step (a) (24.7 g, 0.1 mole) was dissolved in dry dichloromethane (500 ml) and the solution cooled to -15°. A solution of titanium tetrachloride (57.0 g, 21.6 ml, 0.3 mole) in dry dichloromethane (200 ml) was added dropwise with stirring and cooling. To the yellow-orange solution was added -dichloromethyl methyl ether (27.9 g, 22.0 ml, 0.24 mole) in dry dichloromethane (200 ml). The solution was stirred at -15° for 0.5 hr and warmed to room temperature over a period of 2 hr. The reaction mixture was poured onto ice/2N hydrochloric acid (21/500 ml) and stirred vigorously. The dichloromethane layer was separated and the aqueous layer extracted with dichloromethane (2×200 ml). The combined organic extracts were washed with water, dried (Na2SO4) and evaporated. The crude product was recrystallised from 50% aqueous methanol to give an off-white solid (24.0 g) mp 105°-6°. the solution cooled to -15° cooling The solution was stirred at -15° for 0.5 hr The reaction mixture was poured onto ice/2N hydrochloric acid (21/500 ml) stirred vigorously The dichloromethane layer was separated the aqueous layer extracted with dichloromethane (2×200 ml) The combined organic extracts were washed with water dried (Na2SO4) evaporated The crude product was recrystallised from 50% aqueous methanol

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

Procedure: To a solution of 30 g (0.121 mole) of the amide in 254 ml of trifluoroacetic acid at 0° under an argon atmosphere was added dropwise with stirring a solution of 7.5 ml (0.12 mole) of conc. nitric acid in 56 ml of trifluoroacetic acid. The reaction mixture was stirred at 0° for 1/2 hour and at room temperature for 2 hours. The solvents were evaporated. The residue was dissolved in ethyl acetate which was extracted with 5% hydrochloric acid, dilute sodium bicarbonate solution and brine, then dried over anhydrous magnesium sulfate and activated charcoal. After filtering, the solvents were removed to give 34.8 g (98%) of crude (2-trifluoroacetamidoethyl)-3-nitro-4-methoxybenzene which was an amber-colored solid. This material was recrystallized from 400 ml of 1:3 ethyl acetatehexane to give 25.3 g (71.5%) of the product, m.p. 92.5°-93.0°. The mother liquors were concentrated and recrystallized to give a second crop, 4.59 g (13 %), m.p. 90°-92° C. The solvents were evaporated The residue was dissolved in ethyl acetate which was extracted with 5% hydrochloric acid, dilute sodium bicarbonate solution and brine dried over anhydrous magnesium sulfate and activated charcoal After filtering the solvents were removed

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

Procedure: To a solution of 30 g (0.121 mole) of the amide in 254 ml of trifluoroacetic acid at 0° under an argon atmosphere was added dropwise with stirring a solution of 7.5 ml (0.12 mole) of conc. nitric acid in 56 ml of trifluoroacetic acid. The reaction mixture was stirred at 0° for 1/2 hour and at room temperature for 2 hours. The solvents were evaporated. The residue was dissolved in ethyl acetate which was extracted with 5% hydrochloric acid, dilute sodium bicarbonate solution and brine, then dried over anhydrous magnesium sulfate and activated charcoal. After filtering, the solvents were removed to give 34.8 g (98%) of crude (2-trifluoroacetamidoethyl)-3-nitro-4-methoxybenzene which was an amber-colored solid. This material was recrystallized from 400 ml of 1:3 ethyl acetate-hexane to give 25.3 g (71.5%) of the product, m.p. 92.5°-93.0°. The mother liquors were concentrated and recrystallized to give a second crop, 4.59 g (13%), m.p. 90°-92° C. The solvents were evaporated The residue was dissolved in ethyl acetate which was extracted with 5% hydrochloric acid, dilute sodium bicarbonate solution and brine dried over anhydrous magnesium sulfate and activated charcoal After filtering the solvents were removed

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 32.2 ml (0.23 mol) of trifluoroacetic acid were added dropwise to a solution of 22.3 ml (0.15 mol) of 2-(4-methoxyphenyl)ethylamine and 24.7 ml (0.23 mol) of pyridine in 125 ml of absolute THF cooled to 5° C., and the resulting solution was stirred at RT for 3 h. The reaction solution was then poured onto 750 ml of ice, and the deposited precipitate was filtered off with suction and dried at 40° C. in a high vacuum. 36.3 g of the title compound were obtained as a beige solid. the deposited precipitate was filtered off with suction dried at 40° C. in a high vacuum

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

Procedure: The product from step (a) (24.7 g, 0.1 mole) was dissolved in dry dichloromethane (500 ml) and the solution cooled to -15°. A solution of titanium tetrachloride (57.0 g, 21.6 ml, 0.3 mole) in dry dichloromethane (200 ml) was added dropwise with stirring and cooling. To the yellow-orange solution was added -dichloromethyl methyl ether (27.9 g, 22.0 ml, 0.24 mole) in dry dichloromethane (200 ml). The solution was stirred at -15° for 0.5 hr and warmed to room temperature over a period of 2 hr. The reaction mixture was poured onto ice/2N hydrochloric acid (21/500 ml) and stirred vigorously. The dichloromethane layer was separated and the aqueous layer extracted with dichloromethane (2×200 ml). The combined organic extracts were washed with water, dried (Na2SO4) and evaporated. The crude product was recrystallised from 50% aqueous methanol to give an off-white solid (24.0 g) mp 105°-6°. the solution cooled to -15° cooling The solution was stirred at -15° for 0.5 hr The reaction mixture was poured onto ice/2N hydrochloric acid (21/500 ml) stirred vigorously The dichloromethane layer was separated the aqueous layer extracted with dichloromethane (2×200 ml) The combined organic extracts were washed with water dried (Na2SO4) evaporated The crude product was recrystallised from 50% aqueous methanol