5-methoxy-6-(trifluoromethyl)-1H-indole

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

Procedure: The indole (D10) (67.63 g, 0.315 mol) was treated with sodium cyanoborohydride (40 g, 0.637 mol) in glacial acetic acid (500 ml) as in the method of Description 1 to afford the title indoline (67.73 g, 99%) as an off-white solid.

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

Procedure: (5-Methoxy-2-nitro-4-trifluoromethylphenyl)acetonitrile (D9) (85 g, 0.327 mol) in ethanol/water (9:1, 1.6 l) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuo. The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) and the combined organic extract was dried Na2SO4) and evaporated to afford the title indole (67.63 g, 96%) as a grey solid. The reaction mixture was filtered evaporated in vacuo The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) the combined organic extract evaporated

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

Procedure: The indole (D2) (67.63 g, 0.315 mol) in glacial acetic acid (500 ml) was treated with sodium cyanoborohydride (40 g, 0.637 mol) portionwise at room temperature with stirring. After 3 h at room temperature the reaction mixture was diluted with water (500 ml) and basified with 40% aqueous NaOH with cooling. The mixture was then extracted with dichloromethane (3×500 ml) and the combined extracts were dried (Na2SO4) and evaporated to give the title compound (67.73 g, 99%) as an off-white solid. with cooling The mixture was then extracted with dichloromethane (3×500 ml) the combined extracts were dried (Na2SO4) evaporated

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

Procedure: (5-Methoxy-2-nitro-4-trifluoromethylphenyl)acetonitrile (D1) (85 g, 0.327 mol) in ethanol/water (9:1, 1.6 1) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuo. The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) and the combined organic extract was dried (Na2SO4) and evaporated to afford the title indole (67.63 g, 96%) as a grey solid. The reaction mixture was filtered evaporated in vacuo The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) the combined organic extract was dried (Na2SO4) evaporated

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

Procedure: (5-Methoxy-2-nitro-4-trifluoromethylphenyl)acetonitrile (D1) (85 g, 0.327 mol) in ethanol/water (9:1, 1.6 1) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuo. The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) and the combined organic extract was dried (Na2SO4) and evaporated to afford the title indole (67.63 g, 96%) as a grey solid. The reaction mixture was filtered evaporated in vacuo The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) the combined organic extract was dried (Na2SO4) evaporated

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

Procedure: 5 The indole (D8) (67.63 g, 0.315 mol) in glacial acetic acid (500 ml) was treated with sodium cyanoborohydride (40 g, 0.637 mol) at room temperature with stirring. After 3 h at room temperature the reaction mixture was diluted with water (500 ml) and basified with 40% aqueous NaOH with cooling. The mixture was then extracted with dichloromethane (3×500 ml) and the combined extracts were dried (Na2SO4) and evaporated to give the title compound (67.73 g, 99%) as an off-white solid. with cooling The mixture was then extracted with dichloromethane (3×500 ml) the combined extracts were dried (Na2SO4) evaporated

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

Procedure: (5-Methoxy-2-nitro4-trifluoromethylphenyl)acetonitrile (D7) (85 g, 0.327 mol) in ethanol/water (9:1, 1.6 l) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuo. The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) and the combined organic extract was dried (Na2SO4) and evaporated to afford the title indole (67.63 g, 96%) as a grey solid. The reaction mixture was filtered evaporated in vacuo The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) the combined organic extract was dried (Na2SO4) evaporated

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

Procedure: The indole (D10) (67.63 g, 0.315 mol) was treated with sodium cyanoborohydride (40 g, 0.637 mol) in glacial acetic acid (500 ml) as in the method of Description 1 to afford the title indoline (67.73 g, 99%) as an off-white solid

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

Procedure: (5-Methoxy-2-nitro-4-trifluoromethylphenyl)acetonitrile (D9) (85 g, 0.327 mol) in ethanol/water (9:1, 1.6 l) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuo. The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) and the combined organic extract was dried (Na2SO4) and evaporated to afford the title indole (67.63 g, 96%) as a grey solid. The reaction mixture was filtered evaporated in vacuo The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) the combined organic extract was dried (Na2SO4) evaporated

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

Procedure: The indole (D28) (67.63 g, 0.315 mol) was treated with sodium cyanoborohydride (40 g, 0.637 mol) in glacial acetic acid (500 ml) as in the method of Description 16 to afford the title indoline (67.73 g, 99%) as an off-white solid.

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

Procedure: (5-Methoxy-2-nitro-4-trifluoromethylphenyl)acetonitrile (D27) (85g, 0.327 mol) in ethanol/water (9:1, 1.61) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuao. The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) and the combined organic extract was dried (Na2SO4) and evaporated to afford the title indole (67.63 g, 96%) as a grey solid. The reaction mixture was filtered evaporated in vacuao The residue was partitioned between aqueous K2CO3 (1 l) and dichloromethane (2×1 l) the combined organic extract was dried (Na2SO4) evaporated

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

Procedure: The indole (D10) (67.63 g, 0.315 mol) was treated with sodium cyanoborohydride (40 g, 0.637 mol) in glacial acetic acid (500 ml) as in the method of Description 1 to afford the title indoline (67.73 g, 99%) as an off-white solid.