methyl 4-methoxy-1H-indole-6-carboxylate

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

Procedure: Methyl iodide (0.72 mL, 11.5 mmol, 1.1 equiv.) was added dropwise, over 10 minutes, to a stirred solution of 4-hydroxy-1H-indole-6-carboxylic acid methyl ester (2 g, 10.5 mmol, 1 equiv.) and potassium carbonate (1.3 g, 15.7 mmol, 1.5 equiv.) in acetone (20 mL) at room temperature and the mixture was heated at reflux for 16 hours. The solvent was removed under vacuum, the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and the solvent removed under vacuum to afford 4-methoxy-1H-indole-6-carboxylic acid methyl ester, 1.1 g (49% yield). LC @215 nm; Rt 1.23: 91%, m/z (ES+): 206 (M+H+.); δH (400 MHz; MeOD) 7.74 (1H, s), 7.15 (1H, m), 7.03 (1H, d), 6.46 (1H, m), 3.86 (3H, s), 3.80 (3H, s). the mixture was heated at reflux for 16 hours The solvent was removed under vacuum the residue dissolved in ethyl acetate (20 mL) washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL) The organic layer was dried over Na2SO4 the solvent removed under vacuum

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

Procedure: Methyl iodide (0.72 mL, 11.5 mmol, 1.1 equiv.) was added dropwise, over 10 minutes, to a stirred solution of 4-hydroxy-1H-indole-6-carboxylic acid methyl ester (2 g, 10.5 mmol, 1 equiv.) and potassium carbonate (1.3 g, 15.7 mmol, 1.5 equiv.) in acetone (20 mL) at room temperature and the mixture was heated at reflux for 16 hours. The solvent was removed under vacuum, the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and the solvent removed under vacuum to afford 4-methoxy-1H-indole-6-carboxylic acid methyl ester, 1.1 g (49% yield). LC @215 nm; Rt 1.23: 91%, m/z (ES+): 206 (M+H+.); δH (400 MHz; MeOD) 7.74 (1H, s), 7.15 (1H, m), 7.03 (1H, d), 6.46 (1H, m), 3.86 (3H, s), 3.80 (3H, s). the mixture was heated at reflux for 16 hours The solvent was removed under vacuum the residue dissolved in ethyl acetate (20 mL) washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL) The organic layer was dried over Na2SO4 the solvent removed under vacuum

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

Procedure: Methyl iodide (0.72 mL, 11.5 mmol, 1.1 equiv.) was added dropwise, over 10 minutes, to a stirred solution of 4-hydroxy-1H-indole-6-carboxylic acid methyl ester (2 g, 10.5 mmol, 1 equiv.) and potassium carbonate (1.3 g, 15.7 mmol, 1.5 equiv.) in acetone (20 mL) at room temperature and the mixture was heated at reflux for 16 hours. The solvent was removed under vacuum, the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and the solvent removed under vacuum to afford 4-methoxy-1H-indole-6-carboxylic acid methyl ester, 1.1 g (49% yield). LC @215 nm; Rt 1.23: 91%, m/z (ES+): 206 (M+H+.); δH (400 MHz; MeOD) 7.74 (1H, s), 7.15 (1H, m), 7.03 (1H, d), 6.46 (1H, m), 3.86 (3H, s), 3.80 (3H, s). the mixture was heated at reflux for 16 hours The solvent was removed under vacuum the residue dissolved in ethyl acetate (20 mL) washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL) The organic layer was dried over Na2SO4 the solvent removed under vacuum

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

Procedure: Sodium cyanoborohydride (3.6 g, 57.8 mmol, 3 equiv.) was added to a stirred solution of 4-methoxy-1H-indole-6-carboxylic acid methyl ester (3.96 g, 19.3 mmol, 1 equiv.) in acetic acid (40 mL) at room temperature over 5 minutes. The mixture was stirred for 30 minutes, then cooled to 0° C. and slowly poured onto concentrated ammonium hydroxide (78 mL, d=0.880) at 0° C. The mixture was diluted with water (20 mL) extracted with dichloromethane (4×25 mL). The organic layers were combined, dried over Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified by flash column chromatography (SiO2, dichloromethane) and the fractions combined to afford 4-methoxy-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester, 2.8 g (70% yield). LC @215 nm; Rt 0.85: 97%, m/z (ES+): 208 (M+H+.); δH (400 MHz; d6-DMSO) 6.90 (1H, s), 6.86 (1H, s), 3.80 (3H, s), 3.79 (3H, s), 3.49 (2H, t), 2.89 (2H, t). extracted with dichloromethane (4×25 mL) dried over Na2SO4 the solvent was removed under vacuum The crude mixture was purified by flash column chromatography (SiO2, dichloromethane)

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

Procedure: Sodium cyanoborohydride (3.6 g, 57.8 mmol, 3 equiv.) was added to a stirred solution of 4-methoxy-1H-indole-6-carboxylic acid methyl ester (3.96 g, 19.3 mmol, 1 equiv.) in acetic acid (40 mL) at room temperature over 5 minutes. The mixture was stirred for 30 minutes, then cooled to 0° C. and slowly poured onto concentrated ammonium hydroxide (78 mL, d=0.880) at 0° C. The mixture was diluted with water (20 mL) extracted with dichloromethane (4×25 mL). The organic layers were combined, dried over Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified by flash column chromatography (SiO2, dichloromethane) and the fractions combined to afford 4-methoxy-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester, 2.8 g (70% yield). LC @215 nm; Rt 0.85: 97%, m/z (ES+): 208 (M+H+.); δH (400 MHz; d6-DMSO) 6.90 (1H, s), 6.86 (1H, s), 3.80 (3H, s), 3.79 (3H, s), 3.49 (2H, t), 2.89 (2H, t). extracted with dichloromethane (4×25 mL) dried over Na2SO4 the solvent was removed under vacuum The crude mixture was purified by flash column chromatography (SiO2, dichloromethane)