2-(1H-indol-4-yloxy)acetonitrile

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:; See reaction.notes.procedure_details.

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)

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

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)

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

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)

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

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)

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

Procedure: To a solution of 2-(1H-indol-4-yloxy)-acetonitrile (0.9 g, 5.2 mmol) in anhydrous ethyl ether (30 ml) was added lithium aluminum hydride (95%, 0.21 g, 5.2 mmol) at room temperature. The reaction was allowed to reflux for 2 hours, another equivalent of lithium aluminum hydride (0.21 g, 5.2 mmol) was added. The reaction was allowed to reflux for another 2 hours and then was quenched with 1N sodium hydroxide and water. The solid was removed by filtration and the filtrate was concentrated and dissolved in methanol and water. To a above mixture was added 2N hydrochloric acid until pH<3 and then extracted with ethyl ether. To the above aqueous layer was added sodium hydroxide until pH>9, the mixture was extracted with isopropanol-methylene (1:3). The combined organic layers were washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under vacuum to afford 0.3 g (33%) of product as a brown solid. mp: 123-125° C.; MS EI m/e 177 (M+) to reflux for 2 hours to reflux for another 2 hours was quenched with 1N sodium hydroxide and water The solid was removed by filtration the filtrate was concentrated dissolved in methanol To a above mixture was added 2N hydrochloric acid until pH<3 extracted with ethyl ether To the above aqueous layer was added sodium hydroxide until pH>9 the mixture was extracted with isopropanol-methylene (1:3) The combined organic layers were washed with brine dried over anhydrous sodium sulfate The solvent was removed under vacuum

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

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)

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

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)

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

Procedure: A 0° C. solution of 4-hydroxyindole (20 g, 150 mmol) in 500 ml of dimethylformamide is treated with NaH (60% dispersion in mineral oil; 6.6 g, 165 mmol). After 30 minutes, bromoacetonitrile (11.5 ml, 165 mmol) is added, and the resulting mixture is allowed to slowly warm to ambient temperature and stir for 3 days. The reaction mixture is diluted with ethyl acetate and washed 3 times with H2O. The organic layer is dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes) to give 25 g of (1H-indol-4-yloxy)acetonitrile (97%). washed 3 times with H2O The organic layer is dried over Na2SO4 concentrated in vacuo The crude residue is purified by normal phase HPLC (SiO2; 5% step gradient of 0 to 20% ethyl acetate in hexanes)