1H-Indole-2-carboxylic acid, 4-fluoro-, Methyl ester

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

Procedure: To methyl 4-fluoro-1h-indole-2-carboxylate (1.211 mmol, 234 mg) in N,N-dimethylformamide (10 ml) at 0° C. was added sodium hydride (1.817 mmol, 72.7 mg). The reaction mixture was stirred for one hour at room temperature before iodomethane (1.817 mmol, 0.113 ml, 258 mg) was added. After stirring for three hours water was added and the product was extracted with dichloromethane and concentrated in vacuo to give methyl 4-fluoro-1-methyl-1H-indole-2-carboxylate (264 mg). The latter compound was dissolved in ethanol (5 ml). Then 2 N aqueous sodium hydroxide (5.84 mmol, 2.92 ml) and potassium hydroxide (1.168 mmol, 65.5 mg) were added and the reaction mixture was stirred at 80° C. over night. 2N Hydrochloric acid was added to the reaction mixture and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate) and concentrated to give 4-fluoro-1-methyl-1H-indole-2-carboxylic acid (189 mg). was added was added the product was extracted with dichloromethane concentrated in vacuo

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

Procedure: To methyl 4-fluoro-1h-indole-2-carboxylate (1.211 mmol, 234 mg) in N,N-dimethylformamide (10 ml) at 0° C. was added sodium hydride (1.817 mmol, 72.7 mg). The reaction mixture was stirred for one hour at room temperature before iodomethane (1.817 mmol, 0.113 ml, 258 mg) was added. After stirring for three hours water was added and the product was extracted with dichloromethane and concentrated in vacuo to give methyl 4-fluoro-1-methyl-1H-indole-2-carboxylate (264 mg). The latter compound was dissolved in ethanol (5 ml). Then 2 N aqueous sodium hydroxide (5.84 mmol, 2.92 ml) and potassium hydroxide (1.168 mmol, 65.5 mg) were added and the reaction mixture was stirred at 80° C. over night. 2N Hydrochloric acid was added to the reaction mixture and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate) and concentrated to give 4-fluoro-1-methyl-1H-indole-2-carboxylic acid (189 mg). was added was added the product was extracted with dichloromethane concentrated in vacuo

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

Procedure: Using general procedure B, 4-fluoro-1H-indole-2-carboxylic acid methyl ester was coupled with 1-bromomethyl-naphthalene and the product obtained was hydrolyzed to give the title compound as a pale yellow solid. MS: 318.1 ([M−H]−). the product obtained

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

Procedure: Using general procedure B, 4-fluoro-1H-indole-2-carboxylic acid methyl ester was coupled with 1-bromomethyl-naphthalene and the product obtained was hydrolyzed to give the title compound as a pale yellow solid. MS: 318.1 ([M−H]−). the product obtained

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

Procedure: To methyl 4-fluoro-1h-indole-2-carboxylate (1.211 mmol, 234 mg) in N,N-dimethylformamide (10 ml) at 0° C. was added sodium hydride (1.817 mmol, 72.7 mg). The reaction mixture was stirred for one hour at room temperature before iodomethane (1.817 mmol, 0.113 ml, 258 mg) was added. After stirring for three hours water was added and the product was extracted with dichloromethane and concentrated in vacuo to give methyl 4-fluoro-1-methyl-1H-indole-2-carboxylate (264 mg). The latter compound was dissolved in ethanol (5 ml). Then 2 N aqueous sodium hydroxide (5.84 mmol, 2.92 ml) and potassium hydroxide (1.168 mmol, 65.5 mg) were added and the reaction mixture was stirred at 80° C. over night. 2N Hydrochloric acid was added to the reaction mixture and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate) and concentrated to give 4-fluoro-1-methyl-1H-indole-2-carboxylic acid (189 mg). was added was added the product was extracted with dichloromethane concentrated in vacuo

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

Procedure: 25 4-Fluoroindole-2-carboxylic acid (0.65 g, 3.40 mmol) was dissolved in methanol (50 ml), and 4-toluenesulfonic acid (1.4 g, 7.36 mmol) was added under nitrogen. The solution was stirred at reflux for 24 hours. Most of the methanol was removed by evaporation, and the residue was dissolved in dicholoromethane (100 ml), washed with saturated sodium carbonate, and the organic layer was separated. The aqueous layer was extracted with dichloromethane (3×50 ml). The combined organic layers were washed with water, dried over sodium sulphate, and evaporated to yield a yellow crystalline material. at reflux for 24 hours Most of the methanol was removed by evaporation the residue was dissolved in dicholoromethane (100 ml) washed with saturated sodium carbonate the organic layer was separated The aqueous layer was extracted with dichloromethane (3×50 ml) The combined organic layers were washed with water dried over sodium sulphate evaporated to yield a yellow crystalline material

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

Procedure: Using general procedure B, 4-fluoro-1H-indole-2-carboxylic acid methyl ester was coupled with 1-bromomethyl-naphthalene and the product obtained was hydrolyzed to give the title compound as a pale yellow solid. MS: 318.1 ([M−H]−). the product obtained

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

Procedure: To methyl 4-fluoro-1h-indole-2-carboxylate (1.211 mmol, 234 mg) in N,N-dimethylformamide (10 ml) at 0° C. was added sodium hydride (1.817 mmol, 72.7 mg). The reaction mixture was stirred for one hour at room temperature before iodomethane (1.817 mmol, 0.113 ml, 258 mg) was added. After stirring for three hours water was added and the product was extracted with dichloromethane and concentrated in vacuo to give methyl 4-fluoro-1-methyl-1H-indole-2-carboxylate (264 mg). The latter compound was dissolved in ethanol (5 ml). Then 2 N aqueous sodium hydroxide (5.84 mmol, 2.92 ml) and potassium hydroxide (1.168 mmol, 65.5 mg) were added and the reaction mixture was stirred at 80° C. over night. 2N Hydrochloric acid was added to the reaction mixture and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate) and concentrated to give 4-fluoro-1-methyl-1H-indole-2-carboxylic acid (189 mg). was added was added the product was extracted with dichloromethane concentrated in vacuo