tert-butyl 1H-indole-2-carboxylate

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

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

Procedure: The above Boc-indole (3.08 g, 12.5 mmol) and isopropylborate (4.83 mL, 21.9 mmol) are dissolved in anhydrous THF (20 mL) and the solution is cooled at 0° C. While stirring, LDA (12.5 mL, 1.5 M mono-THF complex in cyclohexane, 18.7 mmol) is added dropwise. The mixture is stirred at 0° C. for 15 min and then room temperature for 0.5 h, followed by the addition of HCl (6 N, 3.0 mL, 18 mmol) in an ice-water bath. The organic solvent is removed in vacuo and the residue is suspended in H2O (100 mL) and acidified with HCl (6 N) to pH 4˜5. The precipitate is collected via filtration and washed with water and hexanes and dried in air to provide 1-Boc-6-methoxyindole-2-boronic acid (3.38 g, 93%). The mixture is stirred at 0° C. for 15 min The organic solvent is removed in vacuo The precipitate is collected via filtration washed with water and hexanes dried in air

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

Procedure: The above Boc-indole (3.08 g, 12.5 mmol) and isopropylborate (4.83 mL, 21.9 mmol) are dissolved in anhydrous THF (20 mL) and the solution is cooled at 0° C. While stirring, LDA (12.5 mL, 1.5 M mono-THF complex in cyclohexane, 18.7 mmol) is added dropwise. The mixture is stirred at 0° C. for 15 min and then room temperature for 0.5 h, followed by the addition of HCl (6 N, 3.0 mL, 18 mmol) in an ice-water bath. The organic solvent is removed in vacuo and the residue is suspended in H2O (100 mL) and acidified with HCl (6 N) to pH 4˜5. The precipitate is collected via filtration and washed with water and hexanes and dried in air to provide 1-Boc-6-methoxyindole-2-boronic acid (3.38 g, 93%). The mixture is stirred at 0° C. for 15 min The organic solvent is removed in vacuo The precipitate is collected via filtration washed with water and hexanes dried in air

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

Procedure: The above Boc-indole (3.08 g, 12.5 mmol) and isopropylborate (4.83 mL, 21.9 mmol) are dissolved in anhydrous THF (20 mL) and the solution is cooled at 0° C. While stirring, LDA (12.5 mL, 1.5 M mono-THF complex in cyclohexane, 18.7 mmol) is added dropwise. The mixture is stirred at 0° C. for 15 min and then room temperature for 0.5 h, followed by the addition of HCl (6 N, 3.0 mL, 18 mmol) in an ice-water bath. The organic solvent is removed in vacuo and the residue is suspended in H2O (100 mL) and acidified with HCl (6 N) to pH 4˜5. The precipitate is collected via filtration and washed with water and hexanes and dried in air to provide 1-Boc-6-methoxyindole-2-boronic acid (3.38 g, 93%). The mixture is stirred at 0° C. for 15 min The organic solvent is removed in vacuo The precipitate is collected via filtration washed with water and hexanes dried in air

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

Procedure: The above Boc-indole (3.08 g, 12.5 mmol) and isopropylborate (4.83 mL, 21.9 mmol) are dissolved in anhydrous THF (20 mL) and the solution is cooled at 0° C. While stirring, LDA (12.5 mL, 1.5 M mono-THF complex in cyclohexane, 18.7 mmol) is added dropwise. The mixture is stirred at 0° C. for 15 min and then room temperature for 0.5 h, followed by the addition of HCl (6 N, 3.0 mL, 18 mmol) in an ice-water bath. The organic solvent is removed in vacuo and the residue is suspended in H2O (100 mL) and acidified with HCl (6 N) to pH 4˜5. The precipitate is collected via filtration and washed with water and hexanes and dried in air to provide 1-Boc-6-methoxyindole-2-boronic acid (3.38 g, 93%). The mixture is stirred at 0° C. for 15 min The organic solvent is removed in vacuo The precipitate is collected via filtration washed with water and hexanes dried in air

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.325 g (1.50 mmol) tert-butylindole-2-carboxylate is dissolved in 15 ml absolute DMSO, mixed with 0.184 g (1.64 mmol) potassium-tert-butylate and stirred at 110° C. for 15 min. A solution of 0.576 g (1.50 mmol) [1-bromo-3-(4-octylphenoxy)propan-2-yl]acetate in 15 ml absolute DMSO is added drop-wise. Following 30 minutes of heating at 110° C. and subsequent cooling, hydrolysis is carried out in saturated NaCl solution. Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps with saturated NaCl solution, drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of flash column chromatography (flow agent: petroleum ether/ethyl acetate 99:1) and yields the product as a colorless oil. Following 30 minutes of heating at 110° C. subsequent cooling, hydrolysis Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps with saturated NaCl solution drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of flash column chromatography (flow agent: petroleum ether/ethyl acetate 99:1)

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

Procedure: 1.00 g (6.21 mmol) indole-2-carboxylic acid is dissolved in 15 ml absolute THF, mixed with 1.01 g (6.23 mmol) N,N-carbonyldiimidazole and stirred at room temperature for 1 hour. Thereafter, 0.77 g (6.86 mmol) potassium-tert-butylate and 9.12 g (123 mmol) tert-butanol are added. Following heating under reflux for 6 hours, quenching using 5 ml water, filtrating off, rinsing with THF, drying on sodium sulfate and concentration on the rotary evaporator, a brown solid is obtained as the crude product. Preliminary purification by means of column chromatography on silica gel using a short column with petroleum ether/ethyl acetate 95:5 leaves a white solid which is purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 98:2) and yields the product as a white solid. Following heating under reflux for 6 hours quenching filtrating off rinsing with THF drying on sodium sulfate and concentration on the rotary evaporator a brown solid is obtained as the crude product Preliminary purification by means of column chromatography on silica gel using a short column with petroleum ether/ethyl acetate 95:5 leaves a white solid which is purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 98:2)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold solution of tert-butyl 1H-indole-2-carboxylate (1.15 g, 4.94 mmol, 1 equiv) in dimthylformamide sodium hydride (60% dispersion) (237 mg, 5.92 mmol, 1.2 equiv) was added and the reaction stirred until all the sodium hydride has been consumed. 1-bromo-3-chloropropane (1.46 ml, 14.88 mmol, 3 equiv) was added and the reaction stirred at 60° C. for 16 h. The reaction was partitioned between ethyl acetate and water. The organic layer was further washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified using the Biotage flash chromatography system (SNAP, 50 g cartridge, Rf=0.5, gradient—5%-25% ethyl acetate in hexanes) to afford the title compound as an oil (1.52 g, quant); MS for C16H20ClNO2 m/z 293.12 (M+H)+. has been consumed The reaction was partitioned between ethyl acetate and water The organic layer was further washed with brine dried over MgSO4 filtered concentrated in vacuo The resulting residue was purified

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

Procedure: The above Boc-indole (3.08 g, 12.5 mmol) and isopropylborate (4.83 mL, 21.9 mmol) are dissolved in anhydrous THF (20 mL) and the solution is cooled at 0° C. While stirring, LDA (12.5 mL, 1.5 M mono-THF complex in cyclohexane, 18.7 mmol) is added dropwise. The mixture is stirred at 0° C. for 15 min and then room temperature for 0.5 h, followed by the addition of HCl (6 N, 3.0 mL, 18 mmol) in an ice-water bath. The organic solvent is removed in vacuo and the residue is suspended in H2O (100 mL) and acidified with HCl (6 N) to pH 4˜5. The precipitate is collected via filtration and washed with water and hexanes and dried in air to provide 1-Boc-6-methoxyindole-2-boronic acid (3.38 g, 93%). The mixture is stirred at 0° C. for 15 min The organic solvent is removed in vacuo The precipitate is collected via filtration washed with water and hexanes dried in air

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

Procedure: The above Boc-indole (3.08 g, 12.5 mmol) and isopropylborate (4.83 mL, 21.9 mmol) are dissolved in anhydrous THF (20 mL) and the solution is cooled at 0° C. While stirring, LDA (12.5 mL, 1.5 M mono-THF complex in cyclohexane, 18.7 mmol) is added dropwise. The mixture is stirred at 0° C. for 15 min and then room temperature for 0.5 h, followed by the addition of HCl (6 N, 3.0 mL, 18 mmol) in an ice-water bath. The organic solvent is removed in vacuo and the residue is suspended in H2O (100 mL) and acidified with HCl (6 N) to pH 4˜5. The precipitate is collected via filtration and washed with water and hexanes and dried in air to provide 1-Boc-6-methoxyindole-2-boronic acid (3.38 g, 93%). The mixture is stirred at 0° C. for 15 min The organic solvent is removed in vacuo The precipitate is collected via filtration washed with water and hexanes dried in air

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold solution of tert-butyl 1H-indole-2-carboxylate (1.15 g, 4.94 mmol, 1 equiv) in dimthylformamide sodium hydride (60% dispersion) (237 mg, 5.92 mmol, 1.2 equiv) was added and the reaction stirred until all the sodium hydride has been consumed. 1-bromo-3-chloropropane (1.46 ml, 14.88 mmol, 3 equiv) was added and the reaction stirred at 60° C. for 16 h. The reaction was partitioned between ethyl acetate and water. The organic layer was further washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purifed using the Biotage flash chromatography system (SNAP, 50 g cartridge, Rf=0.5, gradient—5%-25% ethyl acetate in hexanes) to afford the title compound as an oil (1.52 g, quant); MS for C16H20ClNO2 m/z 293.12 (M+H)+. has been consumed The reaction was partitioned between ethyl acetate and water The organic layer was further washed with brine dried over MgSO4 filtered concentrated in vacuo