9H-fluorene-9-carboxamide

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: The compound was prepared substantially in accordance with the procedure detailed in Example 21A, using 9-fluorenecarboxylic acid (6.00 g, 28.5 mmol) and oxalyl chloride (3.5 ml, 39.9 mmol) in 30 ml of toluene to provide a clear oil that was dissolved in Et2O and treated with ammonia. The compound was prepared substantially in accordance with the procedure to provide a clear oil that

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

Procedure: Five hundred g. of 9-carbamoylfluorene was slurried in 13 liters of tetrahydrofuran under nitrogen, and the mixture was stirred and heated to 50°. Fifty ml. of Triton B was added, followed by 131 g. of acrylonitrile. The mixture was stirred at 50° for 6 hours, and 65 g. of additional acrylonitrile and 25 ml. of Triton B were added. The mixture was stirred at 50° overnight. heated to 50° of Triton B was added The mixture was stirred at 50° for 6 hours of Triton B were added The mixture was stirred at 50° overnight

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

Procedure: Five hundred g. of 9-carbamoylfluorene was slurried in 13 liters of tetrahydrofuran under nitrogen, and the mixture was stirred and heated to 50°. Fifty ml. of Triton B was added, followed by 131 g. of acrylonitrile. The mixture was stirred at 50° for 6 hours, and 65 g. of additional acrylonitrile and 25 ml. of Triton B were added. The mixture was stirred at 50° overnight. heated to 50° of Triton B was added The mixture was stirred at 50° for 6 hours of Triton B were added The mixture was stirred at 50° overnight

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

Procedure: One hundred g. of 9-carbamoylfluorene was slurried in 3375 ml. of tetrahydrofuran in a 5-liter flask. The mixture was heated to 45° with stirring, and to it was added 10 ml. of Triton B. The mixture was stirred for 15 minutes at constant temperature, and 26.2 g. of acrylonitrile was then added in one portion. The mixture was stirred at the reflux temperature for 3 hours, and was then allowed to cool to room temperature. The mixture was then concentrated under vacuum to a solid, which was purified as described in Example 1 above to obtain 110 g. of product, analytically identical to the product of Example 1. The mixture was heated to 45° to it was added 10 ml The mixture was stirred for 15 minutes at constant temperature, and 26.2 g The mixture was stirred at the reflux temperature for 3 hours The mixture was then concentrated under vacuum to a solid, which was purified to obtain 110 g

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

Procedure: A 4.2 g. portion of 9-carbamoylfluorene was dissolved in 300 ml. of dioxane at 45° C. To the solution was added 0.4 ml. of Triton B (40% benzyltrimethylammonium hydroxide in methanol) and 1.1 g. of acrylonitrile. The reaction mixture was stirred at 70° C. for one hour and was then allowed to cool to ambient temperature and stand overnight. The dioxane was removed under vacuum, and the remaining oil was taken up in ethyl acetate/water. The layers were separated, and the organic layer was washed three times with water and once with saturated sodium chloride solution. The organic layer was then dried over magnesium sulfate, filtered and evaporated under vacuum to a foam, which was taken up in dichloromethane. The solution was boiled, and hexane was added until crystallization occurred. The mixture was chilled overnight, and the crystals were collected by filtration. The crystals were washed with hexane and dried under vacuum at 40° to obtain 3.2 g. of the desired product, m.p. 148°-152°, with sintering at 143°. at 45° C To the solution was added 0.4 ml to cool to ambient temperature stand overnight The dioxane was removed under vacuum The layers were separated the organic layer was washed three times with water The organic layer was then dried over magnesium sulfate filtered evaporated under vacuum to a foam, which hexane was added until crystallization The mixture was chilled overnight the crystals were collected by filtration The crystals were washed with hexane dried under vacuum at 40° to obtain 3.2 g

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

Procedure: A 4.2 g. portion of 9-carbamoylfluorene was dissolved in 300 ml. of dioxane at 45° C. To the solution was added 0.4 ml. of Triton B (40% benzyltrimethylammonium hydroxide in methanol) and 1.1 g. of acrylonitrile. The reaction mixture was stirred at 70° C. for one hour and was then allowed to cool to ambient temperature and stand overnight. The dioxane was removed under vacuum, and the remaining oil was taken up in ethyl acetate/water. The layers were separated, and the organic layer was washed three times with water and once with saturated sodium chloride solution. The organic layer was then dried over magnesium sulfate, filtered and evaporated under vacuum to a foam, which was taken up in dichloromethane. The solution was boiled, and hexane was added until crystallization occurred. The mixture was chilled overnight, and the crystals were collected by filtration. The crystals were washed with hexane and dried under vacuum at 40° to obtain 3.2 g. of the desired product, m.p. 148°-152°, with sintering at 143°. at 45° C To the solution was added 0.4 ml to cool to ambient temperature stand overnight The dioxane was removed under vacuum The layers were separated the organic layer was washed three times with water The organic layer was then dried over magnesium sulfate filtered evaporated under vacuum to a foam, which hexane was added until crystallization The mixture was chilled overnight the crystals were collected by filtration The crystals were washed with hexane dried under vacuum at 40° to obtain 3.2 g

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 52.3 g. of 9-carbamoylfluorene and 10 ml. of benzyltriethylammonium hydroxide in 700 ml. of tetrahydrofuran was heated at 45° C. for thirty minutes and then cooled to 25° C. The reaction mixture was diluted by addition in one portion of 25.2 g. of ethyl vinyl ketone. The reaction mixture was stirred at 25° C. for sixteen hours and at reflux for three hours. The mixture was cooled, added to 200 g. of ice and extracted with 50% ethyl acetate-diethyl ether. The organic extract was washed with water, with 10% sodium hydroxide, dried and the solvent was removed by evaporation under reduced pressure. The solid residue was crystallized from ethyl acetate and petroleum ether to afford 42.6 g of 9-carbamoyl-9-(3-oxopentyl)fluorene. m.p. 133°-135° C. The reaction mixture was diluted by addition in one portion of 25.2 g at reflux for three hours The mixture was cooled added to 200 g of ice and extracted with 50% ethyl acetate-diethyl ether The organic extract was washed with water, with 10% sodium hydroxide dried the solvent was removed by evaporation under reduced pressure The solid residue was crystallized from ethyl acetate and petroleum ether

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred warm (45° C.) solution of 62.7 g. (0.3 mole) of 9-carbamoylfluorene in 700 ml. of tetrahydrofuran were added in one portion 30 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. The reaction mixture was stirred at 45° C. for fifteen minutes, and was then diluted by dropwise addition of 24.5 g. (0.35 mole) of methyl vinyl ketone. The reaction mixture was heated at reflux for three hours following complete addition, and then it was cooled to about 30° C. and added to 500 g. of ice. The aqueous reaction mixture was extracted several times with 50% diethyl ether in ethyl acetate, and the extracts were combined, washed with water, with 10% aqueous sodium hydroxide, again with water and then dried. Removal of the solvent by evaporation under reduced pressure afforded a solid which, following crystallization from ethyl acetate, was identified as 46.1 g. of 9-carbamoyl-9-(3-oxobutyl)fluorene. m.p. 125°-128° C. was then diluted by dropwise addition of 24.5 g The reaction mixture was heated at reflux for three hours addition it was cooled to about 30° C. added to 500 g The aqueous reaction mixture was extracted several times with 50% diethyl ether in ethyl acetate washed with water, with 10% aqueous sodium hydroxide, again with water dried Removal of the solvent by evaporation under reduced pressure afforded a solid which crystallization from ethyl acetate

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred warm (45° C.) solution of 62.7 g. (0.3 mole) of 9-carbamoylfluorene in 700 ml. of tetrahydrofuran were added in one portion 30 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. The reaction mixture was stirred at 45° C. for fifteen minutes, and was then diluted by dropwise addition of 24.5 g. (0.35 mole) of methyl vinyl ketone. The reaction mixture was heated at reflux for three hours following complete addition, and then it was cooled to about 30° C. and added to 500 g. of ice. The aqueous reaction mixture was extracted several times with 50% diethyl ether in ethyl acetate, and the extracts were combined, washed with water, with 10% aqueous sodium hydroxide, again with water and then dried. Removal of the solvent by evaporation under reduced pressure afforded a solid which, following crystallization from ethyl acetate, was identified as 46.1 g. of 9-carbamoyl-9-(3-oxobutyl)fluorene. m.p. 125°-128° C. was then diluted by dropwise addition of 24.5 g The reaction mixture was heated at reflux for three hours addition it was cooled to about 30° C. added to 500 g The aqueous reaction mixture was extracted several times with 50% diethyl ether in ethyl acetate washed with water, with 10% aqueous sodium hydroxide, again with water dried Removal of the solvent by evaporation under reduced pressure afforded a solid which crystallization from ethyl acetate

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