2-(benzenesulfonyl)benzaldehyde

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: To a solution of 2(5-fluoro-2-methyl-1H-indol-1-yl)acetic acid (1.29 g, 1.49 mmol), 2-(phenylsulfonyl)benzaldehyde (1.50 g, 6.10 mmol) and triethylsilane (4.30 ml, 27.0 mmol) in dichloromethane (40 ml) was added trifluoroacetic acid (1.25 ml, 16.5 mmol) dropwise under N2 at 0° C. over 30 minutes. The reaction was warmed to room temperature and stirred for 2 hours. Saturated aqueous sodium hydrogen carbonate solution was added and the product extracted with dichloromethane. The combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo giving a brown oil which was triturated with petroleum ether (40-60° C.) to give a white solid (1.34 g, 2.88 mmol 52%). the product extracted with dichloromethane The combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo giving a brown oil which was triturated with petroleum ether (40-60° C.) to give a white solid (1.34 g, 2.88 mmol 52%)

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

Procedure: To a solution of 2(5-fluoro-2-methyl-1H-indol-1-yl)acetic acid (1.29 g, 1.49 mmol), 2-(phenylsulfonyl)benzaldehyde (1.50 g, 6.10 mmol) and triethylsilane (4.30 ml, 27.0 mmol) in dichloromethane (40 ml) was added trifluoroacetic acid (1.25 ml, 16.5 mmol) dropwise under N2 at 0° C. over 30 minutes. The reaction was warmed to room temperature and stirred for 2 hours. Saturated aqueous sodium hydrogen carbonate solution was added and the product extracted with dichloromethane. The combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo giving a brown oil which was triturated with petroleum ether (40-60° C.) to give a white solid (1.34 g, 2.88 mmol 52%). the product extracted with dichloromethane The combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo giving a brown oil which was triturated with petroleum ether (40-60° C.) to give a white solid (1.34 g, 2.88 mmol 52%)

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

Procedure: To a solution of 2(5-fluoro-2-methyl-1H-indol-1-yl)acetic acid (1.29 g, 1.49 mmol), 2-(phenylsulfonyl)benzaldehyde (1.50 g, 6.10 mmol) and triethylsilane (4.30 ml, 27.0 mmol) in dichloromethane (40 ml) was added trifluoroacetic acid (1.25 ml, 16.5 mmol) dropwise under N2 at 0° C. over 30 minutes. The reaction was warmed to room temperature and stirred for 2 hours. Saturated aqueous sodium hydrogen carbonate solution was added and the product extracted with dichloromethane. The combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo giving a brown oil which was triturated with petroleum ether (40-60° C.) to give a white solid (1.34 g, 2.88 mmol 52%). the product extracted with dichloromethane The combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo giving a brown oil which was triturated with petroleum ether (40-60° C.) to give a white solid (1.34 g, 2.88 mmol 52%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-fluoro benzaldehyde (5.00 ml, 47.6 mmol) in dimethyl sulfoxide (45 ml) was added benzene sulfinic acid sodium salt (8.60 g, 52.4 mmol) and the resulting mixture heated to 100° C. Upon heating the sulfinic acid salt dissolved. The solution was heated at 100° C. for 3 days. The reaction was cooled to room temperature and water (50 ml) added. This mixture was extracted with ethyl acetate, the combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate: petroleum ether (40-60° C.) to 33% ethyl acetate: petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%). δH (300 MHz, d6-DMSO) 10.68 (1H, s, CHO), 8.26-8.17 (1H, m, Ar), 8.08-7.99 (2H, m, Ar), 7.99-7.89 (3H, m, Ar) and 7.80-7.62 (3H, m, Ar). dissolved The solution was heated at 100° C. for 3 days The reaction was cooled to room temperature This mixture was extracted with ethyl acetate the combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate petroleum ether (40-60° C.) to 33% ethyl acetate: petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-fluoro benzaldehyde (5.00 ml, 47.6 mmol) in dimethyl sulfoxide (45 ml) was added benzene sulfinic acid sodium salt (8.60 g, 52.4 mmol) and the resulting mixture heated to 100° C. Upon heating the sulfinic acid salt dissolved. The solution was heated at 100° C. for 3 days. The reaction was cooled to room temperature and water (50 ml) added. This mixture was extracted with ethyl acetate, the combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate: petroleum ether (40-60° C.) to 33% ethyl acetate: petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%). δH (300 MHz, d6-DMSO) 10.68 (1H, s, CHO), 8.26-8.17 (1H, m, Ar), 8.08-7.99 (2H, m, Ar), 7.99-7.89 (3H, m, Ar) and 7.80-7.62 (3H, m, Ar). dissolved The solution was heated at 100° C. for 3 days The reaction was cooled to room temperature This mixture was extracted with ethyl acetate the combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate petroleum ether (40-60° C.) to 33% ethyl acetate: petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-fluoro benzaldehyde (5.00 ml, 47.6 mmol) in dimethyl sulfoxide (45 ml) was added benzene sulfinic acid sodium salt (8.60 g, 52.4 mmol) and the resulting mixture heated to 100° C. Upon heating the sulfinic acid salt dissolved. The solution was heated at 100° C. for 3 days. The reaction was cooled to room temperature and water (50 ml) added. This mixture was extracted with ethyl acetate, the combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate: petroleum ether (40-60° C.) to 33% ethyl acetate: petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%). δH (300 MHz, d6-DMSO) 10.68 (1H, s, CHO), 8.26-8.17 (1H, m, Ar), 8.08-7.99 (2H, m, Ar), 7.99-7.89 (3H, m, Ar) and 7.80-7.62 (3H, m, Ar). dissolved The solution was heated at 100° C. for 3 days The reaction was cooled to room temperature This mixture was extracted with ethyl acetate the combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate petroleum ether (40-60° C.) to 33% ethyl acetate: petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of triethylsilane (0.71 g), trifluoroacetic acid (0.53 g) and 1,2-dichloroethane (2.0 mL) at −10° C. was treated dropwise with a mixture of (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester (0.091 g), 2-benzenesulfonylbenzaldehyde (0.12 g) and 1,2-dichloroethane (3.0 mL), and the resulting mixture was stirred at −10° C. for 15 minutes and then at room temperature for 2 hours. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and dichloromethane (1:1 to 0:1 by volume) to afford the title compound as a colourless gum (0.17 g). at room temperature for 2 hours washed with saturated aqueous sodium hydrogen carbonate solution dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by column chromatography on silica gel eluting with a mixture of cyclohexane and dichloromethane (1:1 to 0:1 by volume)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-fluoro benzaldehyde (5.00 ml, 47.6 mmol) in dimethyl sulfoxide (45 ml) was added benzene sulfinic acid sodium salt (8.60 g, 52.4 mmol) and the resulting mixture heated to 100° C. Upon heating the sulfinic acid salt dissolved. The solution was heated at 100° C. for 3 days. The reaction was cooled to room temperature and water (50 ml) added. This mixture was extracted with ethyl acetate, the combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate:petroleum ether (40-60° C.) to 33% ethyl acetate:petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%). δH (300 MHz, d6-DMSO) 10.68 (1H, s, CHO), 8.26-8.17 (1H, m, Ar), 8.08-7.99 (2H; m, Ar), 7.99-7.89 (3H, m, Ar) and 7.80-7.62 (3H, m, Ar). dissolved The solution was heated at 100° C. for 3 days The reaction was cooled to room temperature This mixture was extracted with ethyl acetate the combined organic extracts were washed with saturated brine dried over MgSO4 concentrated in vacuo The crude material was purified by flash chromatography on silica eluting with 25% ethyl acetate petroleum ether (40-60° C.) to 33% ethyl acetate:petroleum ether (40-60° C.) to give (4.12 g, 16.7 mmol, 35%)

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

Procedure: Sodium borohydride (690 mg, 18.2 mmol) was added to a solution of 2-(benzenesulfonyl)-benzaldehyde (1.98 g, 8.04 mmol) and methanol (50 mL). The reaction mixture was stirred at room temperature. When vigorous bubbling subsided, the reaction mixture was cooled in an ice-water bath, then carefully quenched with a 1.0 N aqueous solution of HCl (20 mL). The mixture was concentrated to remove methanol, then the residue was diluted with water and extracted three times with ethyl acetate. The combined organic phases were dried over MgSO4, filtered, and concentrated to afford 1.94 g (97%) of (2-benzenesulfonyl-phenyl)-methanol as an oil. This product was used in subsequent steps without further purification. When vigorous bubbling the reaction mixture was cooled in an ice-water bath carefully quenched with a 1.0 N aqueous solution of HCl (20 mL) The mixture was concentrated to remove methanol the residue was diluted with water extracted three times with ethyl acetate The combined organic phases were dried over MgSO4 filtered concentrated