N-(2-bromophenyl)formamide

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:

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

Procedure: To a solution of sodium hydride (content 60%, 360 mg, 9.00 mmol) in tetrahydrofuran (5 mL) was added dropwise a solution of N-(2-bromophenyl)formamide (1.50 g, 7.50 mmol) in tetrahydrofuran (5 mL) while stirring at room temperature under a nitrogen atmosphere, followed by stirring at the same temperature for 30 minutes. The reaction mixture was cooled to −78° C., n-butyllithium (2.67 M solution in hexane, 3.37 mL, 9.00 mmol) was added dropwise thereto, followed by stirring at the same temperature for 30 minutes. To the reaction mixture was further added dropwise a solution of 3,3,5,5-tetramethylcyclohexanone (771 mg, 5.00 mmol) in tetrahydrofuran (1 mL) at the same temperature, followed by stirring at the same temperature for 1 hour and at room temperature for 1 hour. To the reaction mixture were added water (10 mL), thereafter extraction with ethyl acetate was carried out. The organic layer was washed with water and a 5% aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtrated, and concentrated. To the obtained crude crystals was added ethanol (7.7 mL), followed by heating and stirring at 60° C., and after the crystals were dissolved, the mixture was allowed to cool down to room temperature. Upon confirming the precipitation of crystals, water (6 mL) was added to the mixture, followed by stirring for 2 hours. The crystals were collected by filtration and dried to give 947 mg of the title compound as yellow crystals. by stirring at the same temperature for 30 minutes The reaction mixture was cooled to −78° C. by stirring at the same temperature for 30 minutes by stirring at the same temperature for 1 hour and at room temperature for 1 hour extraction with ethyl acetate The organic layer was washed with water a 5% aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate filtrated concentrated To the obtained crude crystals by heating stirring at 60° C. after the crystals were dissolved to cool down to room temperature the precipitation of crystals, water (6 mL) was added to the mixture by stirring for 2 hours The crystals were collected by filtration dried

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

Procedure: To acetic anhydride (74.2 g, 727 mmol) was added formic acid (32.9 mL, 872 mmol) under a nitrogen atmosphere while stirring at room temperature, followed by stirring at 70° C. for 3 hours. The reaction mixture was allowed to cool down to room temperature, and tetrahydrofuran (50 mL) was added. To the solution was added a solution of 2-bromoaniline (50.0 g, 291 mmol) in tetrahydrofuran (50 mL) at room temperature, followed by stirring at the same temperature for 1 hour, and concentration was carried out. To the resultant crude crystals was added ethanol (200 mL), followed by heating and stirring at 60° C. After the crystals dissolved, the mixture was allowed to cool down to room temperature, then water (400 mL) was added, followed by stirring for 3 hours. The precipitated crystals were collected by filtration to give 48.8 g of the title compound as white crystals. by stirring at 70° C. for 3 hours to cool down to room temperature by stirring at the same temperature for 1 hour concentration To the resultant crude crystals was added ethanol (200 mL) by heating stirring at 60° C After the crystals dissolved to cool down to room temperature water (400 mL) was added by stirring for 3 hours The precipitated crystals were collected by filtration

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

Procedure: To acetic anhydride (74.2 g, 727 mmol) was added formic acid (32.9 mL, 872 mmol) under a nitrogen atmosphere while stirring at room temperature, followed by stirring at 70° C. for 3 hours. The reaction mixture was allowed to cool down to room temperature, and tetrahydrofuran (50 mL) was added. To the solution was added a solution of 2-bromoaniline (50.0 g, 291 mmol) in tetrahydrofuran (50 mL) at room temperature, followed by stirring at the same temperature for 1 hour, and concentration was carried out. To the resultant crude crystals was added ethanol (200 mL), followed by heating and stirring at 60° C. After the crystals dissolved, the mixture was allowed to cool down to room temperature, then water (400 mL) was added, followed by stirring for 3 hours. The precipitated crystals were collected by filtration to give 48.8 g of the title compound as white crystals. by stirring at 70° C. for 3 hours to cool down to room temperature by stirring at the same temperature for 1 hour concentration To the resultant crude crystals was added ethanol (200 mL) by heating stirring at 60° C After the crystals dissolved to cool down to room temperature water (400 mL) was added by stirring for 3 hours The precipitated crystals were collected by filtration

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:-100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a sulfonation flask, 7.8 g (0.039 mol) N-(2-bromophenyl)form amide was dissolved in a mixture of 100 ml dry tetrahydrofuran. The solution was cooled to −100° C. and 60 ml (0.096 mol) of n-butyllithium solution (1.6M in hexane) was added over a period of 1 hour in such at manner that the internal temperature remained constant at −100° C. (±2° C.). After stirring for 2.5 hours at −100° to −110° C., 5.3 g (0.048 mmol) of 3-cyclopropylcyclobutan-1-one (prepared as described in Example 7), dissolved in 30 ml of dry tetrahydrofuran, were added over a period of 30 minutes in such a manner that the internal temperature remained constant at −100° C. (±2° C.). After stirring for 3 hours at −78° C., the temperature was elevated to 0° C. in ca. 30 minutes. Concentrated ammonium chloride solution and ethyl acetate were added and the organic phase was washed several times with water. After drying and evaporation of the solvent in a water jet vacuum, the crude material was obtained. Purification was achieved by flash chromatography over silica gel (eluant: hexane/ethyl acetate 1:1). Yield: 2.55 g (23% of theory) of N-[2-(3-cyclopropyl-1-hydroxycyclobutyl)-phenyl]formamide in the form of a resin. remained constant at −100° C. (±2° C.) were added over a period of 30 minutes in such a manner that the internal temperature remained constant at −100° C. (±2° C.) After stirring for 3 hours at −78° C. the temperature was elevated to 0° C. in ca. 30 minutes the organic phase was washed several times with water After drying evaporation of the solvent in a water jet vacuum

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a sulfonation flask, 7.8 g (0.039 mol) N-(2-bromophenyl)formamide was dissolved in a mixture of 150 ml dry tetrahydrofuran and 150 ml dry diethyl ether. The solution was cooled to −70° C. and 25.6 ml (0.041 mol) methyllithium solution (1.6M in diethyl ether) added in 30 minutes in such a manner that the internal temperature remained constant at −70° C. Then the resulting solution was cooled to −100° C. and 25.6 ml (0.041 mol) of n-butyllithium solution (1.6M in hexane) was added in such a manner that the internal temperature remained constant at −100° C. (±2° C.). After stirring for 2 hours at −70 to −75° C., the solution was again cooled to −100° C. and 4.54 g (0.041 mol) 2-cyclopropylcyclobutan-1-one (prepared as described in Example 2) dissolved in 30 ml of dry tetrahydrofuran, was added slowly (20 minutes) at an internal temperature of −100° C. After stirring for 3 hours at −75° C., the temperature was elevated to 0° C. in ca. 30 minutes. After the addition of concentrated ammonium chloride solution, ethyl acetate was added and the organic phase was washed several times with water. After drying and evaporation of the solvent in a water jet vacuum, the crude material was obtained. Purification was achieved by flash chromatography over silica gel (eluant: hexane/ethyl acetate 1:1). Yield: 3.4 g (38% of theory) of N-[2-(2-cyclopropyl-1-hydroxycyclo-butyl)-phenyl]formamide in the form of a slightly yellow liquid. remained constant at −70° C Then the resulting solution was cooled to −100° C. remained constant at −100° C. (±2° C.) the solution was again cooled to −100° C. was added slowly (20 minutes) at an internal temperature of −100° C After stirring for 3 hours at −75° C. the temperature was elevated to 0° C. in ca. 30 minutes was added the organic phase was washed several times with water After drying evaporation of the solvent in a water jet vacuum