(3aS,7aR)-3a,4,7,7a-tetrahydro-2-benzofuran-1,3-dione

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

Procedure: 2-Methyl indole (50 mmol, 6.55 g) and AlCl3 (50 mmol, 7.3 g) were stirred in 500 mL DCE. cis-1,2,3,6-Tetrahydrophthalic anhydride (50 mmol, 7.6 g) was added and the reaction was heated to 65° C. for 6 h. The reaction was carefully quenched with 10 mL water and stirred overnight. The resulting red solid was filtered, washed with water, and dried to give 15 g of the sub-title compound. The reaction was carefully quenched with 10 mL water The resulting red solid was filtered washed with water dried

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

Procedure: 2-Methyl indole (50 mmol, 6.55 g) and AlCl3 (50 mmol, 7.3 g) were stirred in 500 mL DCE. cis-1,2,3,6-Tetrahydrophthalic anhydride (50 mmol, 7.6 g) was added and the reaction was heated to 65° C. for 6 h. The reaction was carefully quenched with 10 mL water and stirred overnight. The resulting red solid was filtered, washed with water, and dried to give 15 g of the sub-title compound. The reaction was carefully quenched with 10 mL water The resulting red solid was filtered washed with water dried

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

Procedure: A mixture of cis-4-cyclohexene-1,2-dicarboxylic anhydride (633 mg; 4.25 mmol), 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (1 g; 4.25 mmol) and n-butanol (10 ml) was heated under reflux for 6 hours. The solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography to give an oily substance. The oily substance was treated with a mixture of 3% hydrogen chloride in isopropanol, and the precipitate was recrystallized from isopropanol to give N-[4-{4-(2-pyrimidinyl)-1-piperazinyl}butyl]-4-cyclohexene-1,2-dicarboximide hydrochloride. M.P., 177°-179° C. was heated under reflux for 6 hours The solvent was removed under reduced pressure the residue was purified by silica gel chromatography to give an oily substance the precipitate was recrystallized from isopropanol

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

Procedure: A mixture of cis-4-cyclohexene-1,2-dicarboxylic anhydride (633 mg; 4.25 mmol), 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (1 g; 4.25 mmol) and n-butanol (10 ml) was heated under reflux for 6 hours. The solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography to give an oily substance. The oily substance was treated with a mixture of 3% hydrogen chloride in isopropanol, and the precipitate was recrystallized from isopropanol to give N-[4-{4-(2-pyrimidinyl)-1-piperazinyl}butyl]-4-cyclohexene-1,2-dicarboximide hydrochloride. M.P., 177°-179° C. was heated under reflux for 6 hours The solvent was removed under reduced pressure the residue was purified by silica gel chromatography to give an oily substance the precipitate was recrystallized from isopropanol

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(2-Aminoethyl)piperidine (2.11 g) was added to cis-4-cyclohexene-1,2-dicarboxylic anhydride (2.50 g) and stirred for 6 hours at 140° C. The reaction mixture was suspended into a mixed solution of 2-propanol (125 ml) and water (21 ml) and then sodium borohydride (3.12 g) was added thereto at room temperature. After being stirred for 68 hours at room temperature, the reaction mixture was acidified with dilute hydrochloric acid and then concentrated. The residue was adjusted to pH 9 with saturated sodium hydrogencarbonate aqueous solution and 1N sodium hydroxide, and then extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate anhydride, and concentrated, thereby yielding a crude (3.34 g) containing the entitled compound as brown syrup. at room temperature After being stirred for 68 hours at room temperature concentrated extracted with ethyl acetate The extract was washed with saturated brine dried over sodium sulfate anhydride concentrated yielding a crude (3.34 g)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Tetradecylamine (3.51 g) was added to cis-4-cyclohexene-1,2-dicarboxylic anhydride (2.50 g) and stirred for 5 hours at 140° C. The reaction mixture was suspended into a mixed solution of 2-propanol (125 ml) and water (21 ml) and then sodium borohydride (3.11 g) was added thereto at room temperature. After being stirred for 67.5 hours at room temperature, the reaction mixture was acidified with dilute hydrochloric acid. The resulting solid was collected by filtration under a vacuum, washed with water, and dried, thereby yielding the entitled compound (5.38 g) as white solid. at room temperature After being stirred for 67.5 hours at room temperature The resulting solid was collected by filtration under a vacuum washed with water dried

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Tetradecylamine (3.51 g) was added to cis-4-cyclohexene-1,2-dicarboxylic anhydride (2.50 g) and stirred for 5 hours at 140° C. The reaction mixture was suspended into a mixed solution of 2-propanol (125 ml) and water (21 ml) and then sodium borohydride (3.11 g) was added thereto at room temperature. After being stirred for 67.5 hours at room temperature, the reaction mixture was acidified with dilute hydrochloric acid. The resulting solid was collected by filtration under a vacuum, washed with water, and dried, thereby yielding the entitled compound (5.38 g) as white solid. at room temperature After being stirred for 67.5 hours at room temperature The resulting solid was collected by filtration under a vacuum washed with water dried

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

Procedure: 16.6 g of p-nitrophenethylamine and 15.1 g of cis-1,2,3,6-tetrahydrophthalic anhydride are heated under reflux in 300 ml of toluene, with stirring and a water trap, for 16 hours. This mixture is cooled and take to dryness by warming under reduced pressure. The residue is transferred to a flask containing 500 ml of water, 270 g ferrous sulfate heptahydrate and 1.3 ml concentrated hydrochloric acid. Steam is delivered to the mixture. When the temperature reaches 90° C., 75 ml of concentrated ammonium hydroxide is added in one portion, and at two-minute intervals three 25 ml portions of ammonium hydroxide are added. Continue stirring and heating during the additions. The total reaction time is 8-10 minutes. Immediately pour the mixture onto 1 kg of cracked ice. The solid is collected by filtration and washed with water. Recrystallize from water ethanol to obtain -4-(cis-1,2,3,6-tetrahydrophthalimidoethyl) aniline (1f). This mixture is cooled by warming under reduced pressure The residue is transferred to a flask reaches 90° C. Continue stirring heating during the additions The total reaction time is 8-10 minutes The solid is collected by filtration washed with water Recrystallize from water ethanol

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 31 g (0.2 mole) of cis-1,2,3,6-tetrahydrophthalic anhydride and 26.2 g (0.2 mole) of 6-aminohexanoic acid are dissolved in 400 ml. of acetic acid and warmed 3 hours on a steam bath. The cooled solution is concentrated to remove most of the acetic acid and the residue taken up in 200 ml. of methylene chloride. The solution is washed twice with water and dried over sodium sulfate. The solvent is removed and the residue taken up in 500 ml toluene. Para-toluenesulfonic acid (1 g) is added to the solution, followed by reflux for 10 hrs. with a Dean-Stark water trap. The solution is cooled and concentrated to about 50 ml and diluted with 50 ml of hexane. The mixture is shaken for a few minutes until the oil crystallizes then cooled at 4° C. for several hours, filtered and dried at 50° C. The light yellow crystals (32 g) are taken up in chloroform and filtered to remove any precipitate. The solution is diluted with hexane near the cloud point, cooled until a crystalline mass accumulates, filtered and dried to yield white crystals, m.p. 85°-87° C. The cooled solution is concentrated to remove most of the acetic acid The solution is washed twice with water dried over sodium sulfate The solvent is removed Para-toluenesulfonic acid (1 g) is added to the solution by reflux for 10 hrs The solution is cooled concentrated to about 50 ml diluted with 50 ml of hexane crystallizes filtered dried at 50° C filtered to remove any precipitate The solution is diluted with hexane near the cloud point cooled until a crystalline mass accumulates filtered dried to yield white crystals, m.p. 85°-87° C.

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

Procedure: 16.6 g of p-nitrophenethylamine and 15.1 g of cis-1,2,3,6-tetrahydrophthalic anhydride are heated under reflux in 300 ml of toluene, with stirring and a water trap, for 16 hours. This mixture is cooled and take to dryness by warming under reduced pressure. The residue is transferred to a flask containing 500 ml of water, 270 g ferrous sulfate heptahydrate and 1.3 ml concentrated hydrochloric acid. Steam is delivered to the mixture. When the temperature reaches 90° C., 75 ml of concentrated ammonium hydroxide is added in one portion, and at two-minute intervals three 25 ml portions of ammonium hydroxide are added. Continue stirring and heating during the additions. The total reaction time is 8-10 minutes. Immediately pour the mixture onto 1 kg of cracked ice. The solid is collected by filtration and washed with water. Recrystallize from water ethanol to obtain -4-(cis-1,2,3,6-tetrahydrophthalimidoethyl) aniline (1f). This mixture is cooled by warming under reduced pressure The residue is transferred to a flask reaches 90° C. Continue stirring heating during the additions The total reaction time is 8-10 minutes The solid is collected by filtration washed with water Recrystallize from water ethanol

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 31 g (0.2 mole) of cis-1,2,3,6-tetrahydrophthalic anhydride and 26.2 g (0.2 mole) of 6-aminohexanoic acid are dissolved in 400 ml. of acetic acid and warmed 3 hours on a steam bath. The cooled solution is concentrated to remove most of the acetic acid and the residue taken up in 200 ml. of methylene chloride. The solution is washed twice with water and dried over sodium sulfate. The solvent is removed and the residue taken up in 500 ml toluene. Para-toluenesulfonic acid (1 g) is added to the solution, followed by reflux for 10 hrs. with a Dean-Stark water trap. The solution is cooled and concentrated to about 50 ml and diluted with 50 ml of hexane. The mixture is shaken for a few minutes until the oil crystallizes then cooled at 4° C. for several hours, filtered and dried at 50° C. The light yellow crystals (32 g) are taken up in chloroform and filtered to remove any precipitate. The solution is diluted with hexane near the cloud point, cooled until a crystalline mass accumulates, filtered and dried to yield white crystals, m.p. 85°-87° C. The cooled solution is concentrated to remove most of the acetic acid The solution is washed twice with water dried over sodium sulfate The solvent is removed Para-toluenesulfonic acid (1 g) is added to the solution by reflux for 10 hrs The solution is cooled concentrated to about 50 ml diluted with 50 ml of hexane crystallizes filtered dried at 50° C filtered to remove any precipitate The solution is diluted with hexane near the cloud point cooled until a crystalline mass accumulates filtered dried to yield white crystals, m.p. 85°-87° C.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 25 g of cis-4-cyclohexene-1,2-dicarboxylic acid anhydride in 140 ml of tetrahydrofuran is instilled in a suspension of 10 g of lithium aluminum hydride in 140 ml of tetrahydrofuran at room temperature and the mixture is then stirred for 3 hours at reflux temperature. It is cooled to 0° C. a mixture of tetrahydrofuran/water (1+1) is instilled slowly, stirred for 30 minutes, mixed with 150 ml of chloroform, filtered and the filtrate is concentrated by evaporation in a vacuum. The residue is distilled at 0.2 mm/Torr and 150° C. on a bulb tube. After recrystallization of the distillate from toluene/pentane, 21 g of cis-1,6-dihydroxymethyl-3-cyclohexene is obtained as colorless crystals, melting point 33°-35° C. at reflux temperature stirred for 30 minutes filtered the filtrate is concentrated by evaporation in a vacuum The residue is distilled at 0.2 mm/Torr and 150° C. on a bulb tube After recrystallization of the distillate from toluene/pentane