1H-indol-2-ylmethanol

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

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

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

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

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

Procedure: A suspension of lithium aluminum hydride (2.0 g, 0.20 mol) in tetrahydrofuran (100 mL) was cooled with stirring to 0° C. under nitrogen. A solution of ethyl indole-2-carboxylate (10.0 g, 0.052 mol) in tetrahydrofuran was added dropwise, maintaining the reaction temperature between 0°-5° C. After 1 h, the reaction was quenched with saturated sodium potassium tartrate solution. The reaction was filtered and the filter cake washed well with tetrahydrofuran. The tetrahydrofuran was evaporated in vacuo and the residue partitioned between ethyl acetate and water. The ethyl acetate solution was washed with water, saturated brine, dried over magnesium sulfate, filtered and freed of solvent. The title compound was obtained as a yellowish solid. NMR (CDCl3): δ8.18 (1H, bs), 7.57 (1H, d, J=8 Hz), 7.35 (1H, d, J=8 Hz), 7.26 (1H, s), 7.18 (1H, dt, J=1, 8 Hz), 7.10 (1H, dt, J=1, 8 Hz), 6.41 (1H, bs), 4.84 (2H, s). was cooled maintaining the reaction temperature between 0°-5° C the reaction was quenched with saturated sodium potassium tartrate solution The reaction was filtered the filter cake washed well with tetrahydrofuran The tetrahydrofuran was evaporated in vacuo the residue partitioned between ethyl acetate and water The ethyl acetate solution was washed with water, saturated brine dried over magnesium sulfate filtered

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

Procedure: A suspension of lithium aluminum hydride (2.0 g, 0.20 mol) in tetrahydrofuran (100 mL) was cooled with stirring to 0° C. under nitrogen. A solution of ethyl indole-2-carboxylate (10.0 g, 0.052 mol) in tetrahydrofuran was added dropwise, maintaining the reaction temperature between 0°-5° C. After 1 h, the reaction was quenched with saturated sodium potassium tartrate solution. The reaction was filtered and the filter cake washed well with tetrahydrofuran. The tetrahydrofuran was evaporated in vacuo and the residue partitioned between ethyl acetate and water. The ethyl acetate solution was washed with water, saturated brine, dried over magnesium sulfate, filtered and freed of solvent. The title compound was obtained as a yellowish solid. NMR (CDCl3): δ8.18 (1H, bs), 7.57 (1H, d, J=8 Hz), 7.35 (1H, d, J=8 Hz), 7.26 (1H, s), 7.18 (1H, dt, J=1, 8 Hz), 7.10 (1H, dt, J=1, 8 Hz), 6.41 (1H, bs), 4.84 (2H, s). was cooled maintaining the reaction temperature between 0°-5° C the reaction was quenched with saturated sodium potassium tartrate solution The reaction was filtered the filter cake washed well with tetrahydrofuran The tetrahydrofuran was evaporated in vacuo the residue partitioned between ethyl acetate and water The ethyl acetate solution was washed with water, saturated brine dried over magnesium sulfate filtered

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

Procedure: A total of 1.76 g of 2-indolemethanol was dissolved in dry CH2Cl2 (20 mL) at room temperature and stirred overnight with MnO2 (2.1 g, 24 mmol). The mixture was filtered through Celite, the filtrate was evaporated under reduced pressure, and the product was purified by flash chromatography (CH2Cl2). Yield: 1.31 g (75%), 1H NMR (CDCl3): δ7.1-7.5 (m, 4H), 7.76 (d, 1H, J=7.8 Hz), 9.41 (br s, 1H), 9.86 (s, 1H).MS EI): m/z 145 (M+). The mixture was filtered through Celite the filtrate was evaporated under reduced pressure the product was purified by flash chromatography (CH2Cl2)

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

Procedure: A total of 1.76 g of 2-indolemethanol was dissolved in dry CH2Cl2 (20 mL) at room temperature and stirred overnight with MnO2 (2.1 g, 24 mmol). The mixture was filtered through Celite, the filtrate was evaporated under reduced pressure, and the product was purified by flash chromatography (CH2Cl2). Yield: 1.31 g (75%), 1H NMR (CDCl3): δ7.1-7.5 (m, 4H), 7.76 (d, 1H, J=7.8 Hz), 9.41 (br s, 1H), 9.86 (s, 1H).MS EI): m/z 145 (M+). The mixture was filtered through Celite the filtrate was evaporated under reduced pressure the product was purified by flash chromatography (CH2Cl2)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 50-mL round-bottom flask, a total of 2.28 g (12 mmol) of ethyl 2-indolecarboxylate was dissolved in 15 mL of dry THF under N2. The solution was cooled to -78° C. (acetone-dry ice bath) and 24 mL (24 mmol) of 1.0M DIBAL in THF was added over a period of 1 h. The mixture was stirred for 2 h at -78° C., quenched with 10 mL of 1N HCl, then allowed to warm to room temperature. The reaction mixture was then extracted with ether (4×100 mL) and the ether layer was washed with 1N HCL (2×100 mL), dried over MgSO4, filtered, and evaporated in vacuo. The product was purified by flash chromatography (1:1 ethyl acetate:petroleum ether). Yield: 1.76 g (99%). 1H NMR (CDCl3): δ1.86 (t, 1H, J=6, OH), 4.82 (d, 2H, J=6), 6.40 (s, 1H), 7.0-7.3 (m, 2H), 7.34 (d, 1H, J=7.8), 7.58 (d, 1H, J=7.8), 8.36 (br s, 1H) MS (EI): m/z 147 (M+). was added over a period of 1 h quenched with 10 mL of 1N HCl to warm to room temperature The reaction mixture was then extracted with ether (4×100 mL) the ether layer was washed with 1N HCL (2×100 mL) dried over MgSO4 filtered evaporated in vacuo The product was purified by flash chromatography (1:1 ethyl acetate:petroleum ether)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 50-mL round-bottom flask, a total of 2.28 g (12 mmol) of ethyl 2-indolecarboxylate was dissolved in 15 mL of dry THF under N2. The solution was cooled to -78° C. (acetone-dry ice bath) and 24 mL (24 mmol) of 1.0M DIBAL in THF was added over a period of 1 h. The mixture was stirred for 2 h at -78° C., quenched with 10 mL of 1N HCl, then allowed to warm to room temperature. The reaction mixture was then extracted with ether (4×100 mL) and the ether layer was washed with 1N HCL (2×100 mL), dried over MgSO4, filtered, and evaporated in vacuo. The product was purified by flash chromatography (1:1 ethyl acetate:petroleum ether). Yield: 1.76 g (99%). 1H NMR (CDCl3): δ1.86 (t, 1H, J=6, OH), 4.82 (d, 2H, J=6), 6.40 (s, 1H), 7.0-7.3 (m, 2H), 7.34 (d, 1H, J=7.8), 7.58 (d, 1H, J=7.8), 8.36 (br s, 1H) MS (EI): m/z 147 (M+). was added over a period of 1 h quenched with 10 mL of 1N HCl to warm to room temperature The reaction mixture was then extracted with ether (4×100 mL) the ether layer was washed with 1N HCL (2×100 mL) dried over MgSO4 filtered evaporated in vacuo The product was purified by flash chromatography (1:1 ethyl acetate:petroleum ether)

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

Procedure: To a stirred solution of crude (1H-indol-2-yl)methanol 17 (5.37 g, 36.53 mmol) in anhydrous CH2Cl2 (50 mL) at cold-bath temperature (˜10° C.) was added portionwise pyridinium chlorochromate (PCC) (9.44 g, 40.18 mmol). Reaction was stirred at ambient temperature for 2 hours. Reaction was diluted with CH2Cl2 and filtered through a pad of celite and washed with CH2Cl2. After evaporation of solvent, crude product was silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 1H-indole-2-carbaldehyde 18 (1.52 g, 29% yield). Reaction Reaction filtered through a pad of celite washed with CH2Cl2 After evaporation of solvent, crude product chromatographed (Biotage)

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

Procedure: To ethyl 1H-indole-2-carboxylate 16 (6.5 g, 34.35 mmol) in THF at 0° C. was added lithium aluminum hydride solution (1M, in THF 1.43 g, 37.78 mmol) dropwise and the reaction mixture was stirred for 3.5 hours at 0° C. The reaction mixture was quenched with H2O, 15% NaOH, and H2O before it was filtered and rinsed with THF. Reaction mixture was dried (anhydrous Na2SO4) and evaporation of the solvent gave 5.37 g (100% yield) of the crude (1H-indol-2-yl)methanol 17 which was used directly in the next step. The reaction mixture was quenched with H2O, 15% NaOH, and H2O before it was filtered rinsed with THF Reaction mixture was dried (anhydrous Na2SO4) and evaporation of the solvent