3-Hydroxy-4-iodobenzonitrile

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: 10.16 g (32.8 mmol) of benzyl (3R)-3-t-butoxycarbonylamino-4-hydroxybutanoate was dissolved in 100 ml of toluene. 10.5 g (42.7 mmol) of 3-hydroxy-4-iodobenzonitrile, 11.2 g (42.7 mmol) of triphenylphosphine and 7.4 g (42.7 mmol) of N,N,N′,N′-tetramethylazodicarboxyamide were added to the solution under cooling with ice, and they were stirred at room temperature overnight. The solvent was distilled off, and the residue was purified by the silica gel column chromatography (volume ratio of hexane:ethyl acetate=2:1) to obtain the title compound. under cooling with ice, and they The solvent was distilled off the residue was purified by the silica gel column chromatography (volume ratio of hexane:ethyl acetate=2:1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.3 g (2.6 mmol) of benzyl 4-[4-[(2S)-3-chloro-2-(t-butoxycarbonylamino)propyl]phenoxy]piperidine-1-carboxylate, 686 mg (2.8 mmol) of 3-hydroxy-4-iodobenzonitrile and 390 mg (2.8 mmol) of potassium carbonate were dissolved in dimethylformamide. The solution was stirred at 65° C. for 4 days, and then treated with ethyl acetate as the extractant in an ordinary manner to obtain the title compound, which was then subjected to the subsequent reaction without further purification.

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.3 g (2.6 mmol) of benzyl 4-[4-[(2S)-3-chloro-2-(t-butoxycarbonylamino)propyl]phenoxy]piperidine-1-carboxylate, 686 mg (2.8 mmol) of 3-hydroxy-4-iodobenzonitrile and 390 mg (2.8 mmol) of potassium carbonate were dissolved in dimethylformamide. The solution was stirred at 65° C. for 4 days, and then treated with ethyl acetate as the extractant in an ordinary manner to obtain the title compound, which was then subjected to the subsequent reaction without further purification.

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

Procedure: 22.3 g (89.7 mmol) of 3-hydroxy-4-iodobenzoic acid was dissolved in 300 ml of tetrahydrofuran. 19.7 ml (206 mmol) of ethyl chloroformate and 28.7 ml (206 mmol) of triethylamine was added to the solution at 0° C. After stirring for 15 minutes, the obtained triethylamine hydrochloride was taken by the filtration. The filtrate was added to 300 ml of tetrahydrofuran solution, in which ammonia had been bubbled, at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was dissolved in 450 ml of dioxane. 17.4 ml (117 mmol) of Trifluoromethanesulfonic anhydride and 21.8 ml (269 mmol) of pyridine were added to the solution at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was treated with chloroform as the extractant by an ordinary method to obtain an oily residue. This residue was dissolved in 180 ml of tetrahydrofuran/methanol (1:1). 90 ml (90.0 mmol) of 1 N aqueous sodium hydroxide solution was added to the solution at room temperature. After stirring under these conditions for 4 hours, the solvent was evaporated under reduced pressure, and the residue was washed with dichloromethane. The residue was acidified with 1 N aqueous hydrogen chloride solution, and treated with ethyl acetate as the extractant by an ordinary method to obtain the crude product, which was purified by the silica gel column chromatography to obtain the title compound. the obtained triethylamine hydrochloride was taken by the filtration The filtrate was added to 300 ml of tetrahydrofuran solution, in which ammonia had been bubbled, at 0° C After stirring at room temperature for 18 hours the solvent was evaporated under reduced pressure The residue was dissolved in 450 ml of dioxane After stirring at room temperature for 18 hours the solvent was evaporated under reduced pressure The residue was treated with chloroform as the extractant by an ordinary method to obtain an oily residue After stirring under these conditions for 4 hours the solvent was evaporated under reduced pressure the residue was washed with dichloromethane treated with ethyl acetate as the extractant by an ordinary method to obtain the crude product, which was purified by the silica gel column chromatography

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

Procedure: 22.3 g (89.7 mmol) of 3-hydroxy-4-iodobenzoic acid was dissolved in 300 ml of tetrahydrofuran. 19.7 ml (206 mmol) of ethyl chloroformate and 28.7 ml (206 mmol) of triethylamine was added to the solution at 0° C. After stirring for 15 minutes, the obtained triethylamine hydrochloride was taken by the filtration. The filtrate was added to 300 ml of tetrahydrofuran solution, in which ammonia had been bubbled, at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was dissolved in 450 ml of dioxane. 17.4 ml (117 mmol) of Trifluoromethanesulfonic anhydride and 21.8 ml (269 mmol) of pyridine were added to the solution at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was treated with chloroform as the extractant by an ordinary method to obtain an oily residue. This residue was dissolved in 180 ml of tetrahydrofuran/methanol (1:1). 90 ml (90.0 mmol) of 1 N aqueous sodium hydroxide solution was added to the solution at room temperature. After stirring under these conditions for 4 hours, the solvent was evaporated under reduced pressure, and the residue was washed with dichloromethane. The residue was acidified with 1 N aqueous hydrogen chloride solution, and treated with ethyl acetate as the extractant by an ordinary method to obtain the crude product, which was purified by the silica gel column chromatography to obtain the title compound. the obtained triethylamine hydrochloride was taken by the filtration The filtrate was added to 300 ml of tetrahydrofuran solution, in which ammonia had been bubbled, at 0° C After stirring at room temperature for 18 hours the solvent was evaporated under reduced pressure The residue was dissolved in 450 ml of dioxane After stirring at room temperature for 18 hours the solvent was evaporated under reduced pressure The residue was treated with chloroform as the extractant by an ordinary method to obtain an oily residue After stirring under these conditions for 4 hours the solvent was evaporated under reduced pressure the residue was washed with dichloromethane treated with ethyl acetate as the extractant by an ordinary method to obtain the crude product, which was purified by the silica gel column chromatography

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

Procedure: 8.29 g (24.3 mmol) of benzyl (4R)-4-t-butoxycarbonylamino-5-chloropentanoate, 6.9 g (28.0 mmol) of 3-hydroxy-4-iodobenzonitrile, 6.9 g (50 mmol) of potassium carbonate and 4.15 g (25 mmol) of potassium iodide were stirred together in 80 ml of DMF at 70° C. for 3 days. The solvent was evaporated, and the crude product obtained by an ordinary method with ethyl acetate as the extracting solvent was purified by the silica gel chromatography (ethyl acetate/hexane) to obtain the title compound. The solvent was evaporated the crude product obtained by an ordinary method with ethyl acetate as the extracting solvent was purified by the silica gel chromatography (ethyl acetate/hexane)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.5 g (82.6 mmol) of t-butyl(2-bromoethyl) carbamate was dissolved in 200 ml of dimethylformamide (DMF). 10.1 g (41.3 mmol) of 3-hydroxy-4-iodobenzonitrile and 5.7 g (41.3 mmol) of potassium carbonate were added to the obtained solution, and they were stirred at 75° C. for 3 hours. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the title compound was obtained.

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

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

Procedure: 8.29 g (24.3 mmol) of benzyl (4R)-4-t-butoxycarbonylamino-5-chloropentanoate, 6.9 g (28.0 mmol) of 3-hydroxy-4-iodobenzonitrile, 6.9 g (50 mmol) of potassium carbonate and 4.15 g (25 mmol) of potassium iodide were stirred together in 80 ml of DMF at 70° C. for 3 days. The solvent was evaporated, and the crude product obtained by an ordinary method with ethyl acetate as the extracting solvent was purified by the silica gel chromatography (ethyl acetate/hexane) to obtain the title compound. The solvent was evaporated the crude product obtained by an ordinary method with ethyl acetate as the extracting solvent was purified by the silica gel chromatography (ethyl acetate/hexane)