cyclooctanecarbaldehyde

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

Procedure: 38.5 mg of N-(9-azabicyclo[3.3.1]nonan-3-yl)xanthene-9-carboxamide hydrochloride and 44.1 mg of cyclooctanecarbaldehyde were suspended in 3 ml of methanol at room temperature, and 1.60 g of sodium triacetoxyborohydride was added thereto, followed by stirring for 12 hours at the same temperature. Saturated aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the obtained residue was purified by preparative thin layer chromatography (Kieselgel™60F254, Art5744 produced by Merck Co.: chloroform/methanol=19/1), and 9.0 mg of the title compound as a white solid was obtained. followed by extraction with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the obtained residue was purified by preparative thin layer chromatography (Kieselgel™60F254, Art5744 produced by Merck Co.: chloroform/methanol=19/1)

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

Procedure: 1.16 g of N-(piperidin-4-yl)xanthene-9-carboxamide hydrochloride and 586 mg of cyclooctanecarbaldehyde were suspended in 60 ml of tetrahydrofuran at room temperature, and 1.60 g of sodium triacetoxyborohydride was added thereto, followed by stirring for 12 hours at the same temperature. Saturated aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform--chloroform/methanol=50/1), and 660 mg of the title compound as a white solid was obtained. followed by extraction with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform--chloroform/methanol=50/1)

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

Procedure: To a solution of cyclooctanecarbaldehyde (5.0 g) in methanol (300 mL) was added Oxone (22 g). The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under vacuum and the residue was diluted with ethyl acetate (300 mL) and washed with 1N aqueous HCl, water, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The reaction mixture was concentrated under vacuum the residue was diluted with ethyl acetate (300 mL) washed with 1N aqueous HCl, water, and brine dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: The title compound was prepared according to the procedure of Example 216, with the modification that cyclooctanecarboxaldehyde (prepared from cyclooctanone according to the procedure given in Example 205, steps a and b) was used in step d instead of cyclohexanecarboxaldehyde and 5-amino-2-methyl-benzoic acid benzyl ester replaced 3-amino-benzoic acid benzyl ester in step f. 1H NMR (300 MHz, d6-DMSO) 12.40 (1H, br s), 12.10 (1H, br s), 9.55 (1H, br s), 8.29 (1H, s), 7.78 (1H, d), 7.20 (1H, d), 4.78 (2H, s), 2.96 (1H, m), 2.45 (3H, s), 2.10-1.53 (29H, m). The acid was converted to the N-methyl-D-glucamine salt and lyophilised from water/dioxan. Found: C, 61.55; H, 8.31; N, 7.60%; C38H58N4O9.1.5 H2O requires: C, 61.52; H, 8.28; N, 7.55%.

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

Procedure: To a solution of cyclooctanecarbaldehyde (5.0 g) in methanol (300 mL) was added Oxone (22 g). The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under vacuum and the residue was diluted with ethyl acetate (300 mL) and washed with 1N aqueous HCl, water, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The reaction mixture was concentrated under vacuum the residue was diluted with ethyl acetate (300 mL) washed with 1N aqueous HCl, water, and brine dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: 38.5 mg of N-(9-azabicyclo[3.3.1]nonan-3-yl)xanthene-9-carboxamide hydrochloride and 44.1 mg of cyclooctanecarbaldehyde were suspended in 3 ml of methanol at room temperature, and 1.60 g of sodium triacetoxyborohydride was added thereto, followed by stirring for 12 hours at the same temperature. Saturated aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the obtained residue was purified by preparative thin layer chromatography (Kieselgel™60F254, Art5744 produced by Merck Co.: chloroform/methanol=19/1), and 9.0 mg of the title compound as a white solid was obtained. followed by extraction with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the obtained residue was purified by preparative thin layer chromatography (Kieselgel™60F254, Art5744 produced by Merck Co.: chloroform/methanol=19/1)

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

Procedure: 1.16 g of N-(piperidin-4-yl)xanthene-9-carboxamide hydrochloride and 586 mg of cyclooctanecarbaldehyde were suspended in 60 ml of tetrahydrofuran at room temperature, and 1.60 g of sodium triacetoxyborohydride was added thereto, followed by stirring for 12 hours at the same temperature. Saturated aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform--chloroform/methanol=50/1), and 660 mg of the title compound as a white solid was obtained. followed by extraction with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform--chloroform/methanol=50/1)

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

Procedure: To a solution of cyclooctanecarbaldehyde (5.0 g) in methanol (300 mL) was added Oxone (22 g). The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under vacuum and the residue was diluted with ethyl acetate (300 mL) and washed with 1N aqueous HCl, water, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The reaction mixture was concentrated under vacuum the residue was diluted with ethyl acetate (300 mL) washed with 1N aqueous HCl, water, and brine dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: To a solution of cyclooctanecarbaldehyde (5.0 g) in methanol (300 mL) was added Oxone (22 g). The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under vacuum and the residue was diluted with ethyl acetate (300 mL) and washed with 1N aqueous HCl, water, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The reaction mixture was concentrated under vacuum the residue was diluted with ethyl acetate (300 mL) washed with 1N aqueous HCl, water, and brine dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: Cyclooctane carboxaldehyde (14.72 g, 0.105 mole) was added dropwise to a stirred and refluxing mixture of 13.7 g (0.1 mole) p-aminobenzoic acid, 25 g zinc dust, 25 ml glacial acetic acid and 125 ml of benzene. Water which evolved was collected in a Dean-Stark trap as the reaction mass was refluxed overnight. Following the reflux period, the resulting product mass was filtered while still hot. Upon cooling the filtrate, crystals formed therein. The benzene was evaporated and the residue recrystallized from acetonitrile. The crude product weighed 18.77 g. It was decolorized and recrystallized from benzene. The resulting purified 4-[(cyclooctylmethyl)amino]benzoic acid product weighed 12.93 g. It had a melting point of 160°-162° C. refluxing Water which evolved was collected in a Dean-Stark trap as the reaction mass was refluxed overnight the resulting product mass was filtered while still hot Upon cooling the filtrate, crystals formed The benzene was evaporated the residue recrystallized from acetonitrile recrystallized from benzene The resulting purified 4-[(cyclooctylmethyl)amino]benzoic acid product

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

Procedure: Cyclooctane carboxaldehyde (14.72 g, 0.105 mole) was added dropwise to a stirred and refluxing mixture of 13.7 g (0.1 mole) p-aminobenzoic acid, 25 g zinc dust, 25 ml glacial acetic acid and 125 ml of benzene. Water which evolved was collected in a Dean-Stark trap as the reaction mass was refluxed overnight. Following the reflux period, the resulting product mass was filtered while still hot. Upon cooling the filtrate, crystals formed therein. The benzene was evaporated and the residue recrystallized from acetonitrile. The crude product weighed 18.77 g. It was decolorized and recrystallized from benzene. The resulting purified 4-[(cyclooctylmethyl)amino]benzoic acid product weighed 12.93 g. It had a melting point of 160°-162° C. refluxing Water which evolved was collected in a Dean-Stark trap as the reaction mass was refluxed overnight the resulting product mass was filtered while still hot Upon cooling the filtrate, crystals formed The benzene was evaporated the residue recrystallized from acetonitrile recrystallized from benzene The resulting purified 4-[(cyclooctylmethyl)amino]benzoic acid product

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

Procedure: The title compound was prepared according to the procedure of Example 216, with the modification that cyclooctanecarboxaldehyde (prepared from cyclooctanone according to the procedure given in Example 205, steps a and b) was used in step d instead of cyclohexanecarboxaldehyde and 5-amino-2-methyl-benzoic acid benzyl ester replaced 3-amino-benzoic acid benzyl ester in step f. 1H NMR (300 MHz, d6-DMSO) 12.40 (1H, br s), 12.10 (1H, br s), 9.55 (1H, br s), 8.29 (1H, s), 7.78 (1H, d), 7.20 (1H, d), 4.78 (2H, s), 2.96 (1H, m), 2.45 (3H, s), 2.10-1.53 (29H, m). The acid was converted to the N-methyl-D-glucamine salt and lyophilised from water/dioxan. Found: C, 61.55; H, 8.31; N, 7.60%; C38H58N4O9.1.5 H2O requires: C, 61.52; H, 8.28; N, 7.55%.