2-Trifluoromethylindole

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8.6 g of 2-trifluoromethyl-(1H)-indole and 100 ml of tetrahydrofuran were mixed together under an inert atmosphere and cooled to 0° C. Over 15 minutes, about 2.4 g of a suspension of sodium hydride at 50% in oil was added in small fractions and 6.5 ml of benzyl bromide in solution in 10 ml of tetrahydrofuran were introduced over 5 minutes. The mixture was stirred for 42 hours at ambient temperature and then was poured into water saturated with monosodium phosphate. The mixture was extracted with ethyl ether, and the extracts were dried and concentrated to dryness by distillation under reduced pressure. The residue was chromatographed over silica and eluted with a mixture of hexane and ethyl acetate (9/1) to obtain 12.54 g of 1-benzyl-2-trifluoromethyl-(1H)-indole melting at approx. 20° C. were introduced over 5 minutes The mixture was extracted with ethyl ether the extracts were dried concentrated to dryness by distillation under reduced pressure The residue was chromatographed over silica eluted with a mixture of hexane and ethyl acetate (9/1)

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

Procedure: 8.57 g of 2-trifluoromethyl-1H-indole described in J. Org. Chem. (1983) 48-3233 and 10 ml of tetrahydrofuran were mixed together under an inert atmosphere at +5° C. and after 15 minutes, 2.4 g of sodium hydride in oil were added. After 2 minutes, 4.5 ml of 2-bromo-propyne were introduced and the resulting mixture was stirred for 30 minutes at +5° C., then for one hour at 25° C. Another 4.5 ml of bromo-propyne were added and the mixture was stirred for 4 hours and then poured into an iced solution of monosodium phosphate and extracted with ethyl ether. The extracts were concentrated to dryness by distillation under reduced pressure and the residue was chromatographed over silica and eluted with a mixture of hexane and ethyl acetate (95/5) to obtain 8.88 g of 1-(2-propynyl)-2-trifluoromethyl-(1H)-indole melting at 59° C. for one hour at 25° C the mixture was stirred for 4 hours extracted with ethyl ether The extracts were concentrated to dryness by distillation under reduced pressure the residue was chromatographed over silica eluted with a mixture of hexane and ethyl acetate (95/5)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.1 g of aluminum chloride and 20 ml of methylene chloride were mixed together at -65° C. under an inert atmosphere and a solution of 4.61 g of 2-trifluoromethyl-(1H)-indole (J. Org. Chem., 1974 Vol. 39, p. 1836), 1.4 ml of nitromethane and 20 ml of methylene chloride were added at -60° C. 3.3 ml of dichloromethyl ether in solution in 10 ml of methylene chloride were added to the suspension of the resulting mixture was stirred for 15 minutes at -65° C. The temperature was allowed to rise and at about -10° C., a strong evolution of hydrochloric acid was observed which ceased at about 0° C. The black solution obtained was stirred for 30 minutes at 25° C. and the reaction mixture was poured into water and extracted with methylene chloride. The organic phases were washed with an aqueous solution of sodium bicarbonate, then with water and concentrated to dryness under reduced pressure to obtain 4.6 g of 2-trifluoromethyl-3-formyl-(1H)-indole. to rise and at about -10° C. ceased at about 0° C The black solution obtained was stirred for 30 minutes at 25° C. extracted with methylene chloride The organic phases were washed with an aqueous solution of sodium bicarbonate with water and concentrated to dryness under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8.6 g of 2-trifluoromethyl-(1H)-indole and 100 ml of tetrahydrofuran were mixed together under an inert atmosphere and cooled to 0° C. Over 15 minutes, about 2.4 g of a suspension of sodium hydride at 50% in oil was added in small fractions and 6.5 ml of benzyl bromide in solution in 10 ml of tetrahydrofuran were introduced over 5 minutes. The mixture was stirred for 42 hours at ambient temperature and then was poured into water saturated with monosodium phosphate. The mixture was extracted with ethyl ether, and the extracts were dried and concentrated to dryness by distillation under reduced pressure. The residue was chromatographed over silica and eluted with a mixture of hexane and ethyl acetate (9/1) to obtain 12.54 g of 1-benzyl-2-trifluoromethyl-(1H)-indole melting at approx. 20° C. were introduced over 5 minutes The mixture was extracted with ethyl ether the extracts were dried concentrated to dryness by distillation under reduced pressure The residue was chromatographed over silica eluted with a mixture of hexane and ethyl acetate (9/1)

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

Procedure: 8.57 g of 2-trifluoromethyl-1H-indole described in J. Org. Chem. (1983) 48-3233 and 10 ml of tetrahydrofuran were mixed together under an inert atmosphere at +5° C. and after 15 minutes, 2.4 g of sodium hydride in oil were added. After 2 minutes, 4.5 ml of 2-bromo-propyne were introduced and the resulting mixture was stirred for 30 minutes at +5° C., then for one hour at 25° C. Another 4.5 ml of bromo-propyne were added and the mixture was stirred for 4 hours and then poured into an iced solution of monosodium phosphate and extracted with ethyl ether. The extracts were concentrated to dryness by distillation under reduced pressure and the residue was chromatographed over silica and eluted with a mixture of hexane and ethyl acetate (95/5) to obtain 8.88 g of 1-(2-propynyl)-2-trifluoromethyl-(1H)-indole melting at 59° C. for one hour at 25° C the mixture was stirred for 4 hours extracted with ethyl ether The extracts were concentrated to dryness by distillation under reduced pressure the residue was chromatographed over silica eluted with a mixture of hexane and ethyl acetate (95/5)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.1 g of aluminum chloride and 20 ml of methylene chloride were mixed together at -65° C. under an inert atmosphere and a solution of 4.61 g of 2-trifluoromethyl-(1H)-indole (J. Org. Chem., 1974 Vol. 39, p. 1836), 1.4 ml of nitromethane and 20 ml of methylene chloride were added at -60° C. 3.3 ml of dichloromethyl ether in solution in 10 ml of methylene chloride were added to the suspension of the resulting mixture was stirred for 15 minutes at -65° C. The temperature was allowed to rise and at about -10° C., a strong evolution of hydrochloric acid was observed which ceased at about 0° C. The black solution obtained was stirred for 30 minutes at 25° C. and the reaction mixture was poured into water and extracted with methylene chloride. The organic phases were washed with an aqueous solution of sodium bicarbonate, then with water and concentrated to dryness under reduced pressure to obtain 4.6 g of 2-trifluoromethyl-3-formyl-(1H)-indole. to rise and at about -10° C. ceased at about 0° C The black solution obtained was stirred for 30 minutes at 25° C. extracted with methylene chloride The organic phases were washed with an aqueous solution of sodium bicarbonate with water and concentrated to dryness under reduced pressure

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

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

Procedure: A 2.5 M solution of n-butyl lithium in hexanes (8.8 mL, 22 mmole) at room temperature, under N2, is treated with N,N,N'N'-tetramethylethylenediamine (TMEDA) (3.3 mL, 22 mole), stirred at room temperature for 0.5 hour, treated with N-trimethylsilyl-o-toluidine (1.79 g, 10 mmole), heated at reflux temperature for 6 hours, cooled to -78° C., treated with ethyl trifluoroacetate (1.4 mL, 12 mmole) stirred at -78° C. for 0.25 hour, warmed to room temperature, diluted with water and extracted with diethyl ether. The combined extracts are washed sequentially with 1 N HCl and saturated NaHCO3, dried over MgSO4 and concentrated in vacuo to give a residue. The residue is chromatographed using silica gel and 4:1 hexanes:ethyl acetate as eluent to afford the title product as a light yellow solid, mp 104°-106° C. (literature mp 102° C.1), 0.81 g (47% yield), further identified by IR, 1HNMR and 19FNMR analyses. heated at reflux temperature for 6 hours cooled to -78° C. stirred at -78° C. for 0.25 hour warmed to room temperature extracted with diethyl ether The combined extracts are washed sequentially with 1 N HCl and saturated NaHCO3 dried over MgSO4 concentrated in vacuo to give a residue The residue is chromatographed

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.1 g of aluminum chloride and 20 ml of methylene chloride were mixed together at -65° C. under an inert atmosphere and a solution of 4.61 g of 2-trifluoromethyl-(1H)-indole (J. Org. Chem., 1974 Vol. 39, p. 1836), 1.4 ml of nitromethane and 20 ml of methylene chloride were added at -60° C. 3.3 ml of dichloromethyl ether in solution in 10 ml of methylene chloride were added to the suspension of the resulting mixture was stirred for 15 minutes at -65° C. The temperature was allowed to rise and at about -10° C., a strong evolution of hydrochloric acid was observed which ceased at about 0° C. The black solution obtained was stirred for 30 minutes at 25° C. and the reaction mixture was poured into water and extracted with methylene chloride. The organic phases were washed with an aqueous solution of sodium bicarbonate, then with water and concentrated to dryness under reduced pressure to obtain 4.6 g of 2-trifluoromethyl-3-formyl-(1H)-indole. to rise and at about -10° C. ceased at about 0° C The black solution obtained was stirred for 30 minutes at 25° C. extracted with methylene chloride The organic phases were washed with an aqueous solution of sodium bicarbonate with water and concentrated to dryness under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8.6 g of 2-trifluoromethyl-(1H)-indole and 100 ml of tetrahydrofuran were mixed together under an inert atmosphere and cooled to 0° C. Over 15 minutes, about 2.4 g of a suspension of sodium hydride at 50% in oil was added in small fractions and 6.5 ml of benzyl bromide in solution in 10 ml of tetrahydrofuran were introduced over 5 minutes. The mixture was stirred for 42 hours at ambient temperature and then was poured into water saturated with monosodium phosphate. The mixture was extracted with ethyl ether, and the extracts were dried and concentrated to dryness by distillation under reduced pressure. The residue was chromatographed over silica and eluted with a mixture of hexane and ethyl acetate (9/1) to obtain 12.54 g of 1-benzyl-2-trifluoromethyl-(1H)-indole melting at approx. 20° C. were introduced over 5 minutes The mixture was extracted with ethyl ether the extracts were dried concentrated to dryness by distillation under reduced pressure The residue was chromatographed over silica eluted with a mixture of hexane and ethyl acetate (9/1)

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

Procedure: 8.57 g of 2-trifluoromethyl-1H-indole described in J. Org. Chem. (1983) 48-3233 and 10 ml of tetrahydrofuran were mixed together under an inert atmosphere at +5° C. and after 15 minutes, 2.4 g of sodium hydride in oil were added. After 2 minutes, 4.5 ml of 2-bromo-propyne were introduced and the resulting mixture was stirred for 30 minutes at +5° C., then for one hour at 25° C. Another 4.5 ml of bromo-propyne were added and the mixture was stirred for 4 hours and then poured into an iced solution of monosodium phosphate and extracted with ethyl ether. The extracts were concentrated to dryness by distillation under reduced pressure and the residue was chromatographed over silica and eluted with a mixture of hexane and ethyl acetate (95/5) to obtain 8.88 g of 1-(2-propynyl)-2-trifluoromethyl-(1H)-indole melting at 59° C. for one hour at 25° C the mixture was stirred for 4 hours extracted with ethyl ether The extracts were concentrated to dryness by distillation under reduced pressure the residue was chromatographed over silica eluted with a mixture of hexane and ethyl acetate (95/5)