5-chloro-N-cyclohexylpentanamide

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

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

Conditions: temp:18.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of N-cyclohexyl-5-chloropentanamide (4.36 g, 0.020 mol) in benzene (30 ml) at 0° C. was treated with phosphorous pentachloride (4.4 g, 0.021 mol) in portions over 10 minutes. When the addition was complete the reaction was stirred for an additional 2 hours at 18° C. The solution was then cooled to 0° C. and treated with a solution of hydrazoic acid (0.04 mol) in benzene (50 ml) (prepared according to the method described in Reagents for Organic Synthesis, Volume 1, L. F. Fieser and M. Fieser, John Wiley and Sons (New York: 1967). The resulting solution was stirred at 0° C. for an additional 1.5 hours and at 18° C. for 48 hours and then heated under reflux for an additional 3 hours. The solvent was evaporated off under reduced pressure and the resulting residue was dissolved in ethyl acetate (250 ml). The resulting solution was washed with saturated aqueous sodium hydrogen carbonate (3×100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to yield a crude product. The crude product was purified by recrystallization from ethyl acetate-hexane to yield 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole as a colorless crystalline solid, having a melting point of 50°-51° C. and the following physical characteristics: When the addition The solution was then cooled to 0° C. prepared described in Reagents for Organic Synthesis, Volume 1, L The resulting solution was stirred at 0° C. for an additional 1.5 hours and at 18° C. for 48 hours heated under reflux for an additional 3 hours The solvent was evaporated off under reduced pressure the resulting residue was dissolved in ethyl acetate (250 ml) The resulting solution was washed with saturated aqueous sodium hydrogen carbonate (3×100 ml) dried over anhydrous sodium sulfate filtered concentrated under reduced pressure to yield a crude product The crude product was purified by recrystallization from ethyl acetate-hexane

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

Procedure: A stirred solution of 5-chlorovaleryl chloride (50.0 g, 0.322 mol) in dichloromethane (300 ml) at 0° C. was treated dropwise with a solution containing cyclohexylamine (31.68 g, 0.320 mol), triethylamine (32.32 g, 0.320 mol) and dimethylaminopyridine (0.02 g) in dichloromethane (300 ml). The resulting solution was stirred for 2 hours at 0° C. and then for an additional 16 hours at room temperature. The solution was diluted with dichloromethane (400 ml), washed with water (3×200ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure to yield a crude product. The crude product was recrystallized from ethyl acetate-hexane to yield N-cyclohexyl-5-chloropentanamide as a colorless crystalline solid, having a melting point of 70°-71° C. and the following physical characteristics: for an additional 16 hours at room temperature washed with water (3×200ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) dried over anhydrous sodium sulfate The solvent was evaporated off under reduced pressure to yield a crude product The crude product was recrystallized from ethyl acetate-hexane

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

Procedure: A stirred solution of 5-chlorovaleryl chloride (50.0 g, 0.322 mol) in dichloromethane (300 ml) at 0° C. was treated dropwise with a solution containing cyclohexylamine (31.68 g, 0.320 mol), triethylamine (32.32 g, 0.320 mol) and dimethylaminopyridine (0.02 g) in dichloromethane (300 ml). The resulting solution was stirred for 2 hours at 0° C. and then for an additional 16 hours at room temperature. The solution was diluted with dichloromethane (400 ml), washed with water (3×200ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure to yield a crude product. The crude product was recrystallized from ethyl acetate-hexane to yield N-cyclohexyl-5-chloropentanamide as a colorless crystalline solid, having a melting point of 70°-71° C. and the following physical characteristics: for an additional 16 hours at room temperature washed with water (3×200ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) dried over anhydrous sodium sulfate The solvent was evaporated off under reduced pressure to yield a crude product The crude product was recrystallized from ethyl acetate-hexane

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

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

Procedure: Take up the 5-chloro-pentanoic acid cyclohexylamide in THF (700 mL), add sodium hydride (31 g, 60% dispersion on mineral oil, 775 mmol) and heat at 70° C. 19 h. Cool the mixture, filter through a fritted funnel, wash the filtrate with brine, dry the organic layer over sodium sulfate and evaporate. Purify the residue by column chromatography on silica gel (eluting 50% to 100% ethyl acetate) to obtain 1-cyclohexyl-piperidin-2-one as a beige solid (8.8 g, 63%). MS (EI) m/z=181 (M+). 19 h Cool the mixture filter through a fritted funnel wash the filtrate with brine dry the organic layer over sodium sulfate evaporate Purify the residue by column chromatography on silica gel (eluting 50% to 100% ethyl acetate)

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

Procedure: Dissolve cyclohexylamine (8.86 mL, 77.5 mmol) in dichloromethane (700 mL), cool to 0° C. and add 5-chloropentanoyl chloride (10 mL, 77.5 mmol). After 6 h, wash the mixture with 1N HCl and saturated aqueous sodium bicarbonate and brine, dry the organic layer over sodium sulfate and evaporate to a white solid to obtain 5-chloro-pentanoic acid cyclohexylamide: MS (EI) m/z=217 (M+). wash the mixture with 1N HCl and saturated aqueous sodium bicarbonate and brine dry the organic layer over sodium sulfate evaporate to a white solid

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

Procedure: Add NaH (550 g, 14 mmol) into a solution of 5-chloro-N-cyclohexylpentanamide (3 g, 14 mmol) in acetonitrile (100 mL). Stir the reaction at room temperature for 12 hours. Add NaH (1 g, 28 mmol) and continue to stir for 2 days. Pour the reaction into ice and water. Wash the reaction with brine, dry with sodium sulfate, filter and concentrate. Purify the residue by column chromatography to afford the title compound (1.5 g, 60%) as a white solid. 1H NMR (CDCl3): 4.44-4.54 (m, 1H), 3.14 (m, 2H), 2.36-2.42 (m, 2H), 1.70-1.84 (m, 6H), 1.60-1.70 (m, 4H), 1.32-1.48 (m, 4H), 1.00-1.12 (m, 1H). the reaction at room temperature for 12 hours to stir for 2 days Pour Wash the reaction with brine dry with sodium sulfate filter concentrate Purify the residue by column chromatography

Conditions: temp:18.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of N-cyclohexyl-5-chloropentanamide (4.36 g, 0.020 mol) in benzene (30 ml) at 0° C. was treated with phosphorous pentachloride (4.4 g, 0.021 mol) in portions over 10 minutes. When the addition was complete the reaction was stirred for an additional 2 hours at 18° C. The solution was then cooled to 0° C. and treated with a solution of hydrazoic acid (0.04 mol) in benzene (50 ml) (prepared according to the method described in Reagents for Organic Synthesis, Volume 1, L. F. Fieser and M. Fieser, John Wiley and Sons (New York: 1967). The resulting solution was stirred at 0° C. for an additional 1.5 hours and at 18° C. for 48 hours and then heated under reflux for an additional 3 hours. The solvent was evaporated off under reduced pressure and the resulting residue was dissolved in ethyl acetate (250 ml). The resulting solution was washed with saturated aqueous sodium hydrogen carbonate (3×100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to yield a crude product. The crude product was purified by recrystallization from ethyl acetate-hexane to yield 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole as a colorless crystalline solid, having a melting point of 50°-51° C. and the following physical characteristics: When the addition The solution was then cooled to 0° C. prepared described in Reagents for Organic Synthesis, Volume 1, L The resulting solution was stirred at 0° C. for an additional 1.5 hours and at 18° C. for 48 hours heated under reflux for an additional 3 hours The solvent was evaporated off under reduced pressure the resulting residue was dissolved in ethyl acetate (250 ml) The resulting solution was washed with saturated aqueous sodium hydrogen carbonate (3×100 ml) dried over anhydrous sodium sulfate filtered concentrated under reduced pressure to yield a crude product The crude product was purified by recrystallization from ethyl acetate-hexane

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

Procedure: A stirred solution of 5-chlorovaleryl chloride (50.0 g, 0.322 mol) in dichloromethane (300 ml) at 0° C. was treated dropwise with a solution containing cyclohexylamine (31.68 g, 0.320 mol), triethylamine (32.32 g, 0.320 mol) and dimethylaminopyridine (0.02 g) in dichloromethane (300 ml). The resulting solution was stirred for 2 hours at 0° C. and then for an additional 16 hours at room temperature. The solution was diluted with dichloromethane (400 ml), washed with water (3×200 ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure to yield a crude product. The crude product was recrystallized from ethyl acetate-hexane to yield N-cyclohexyl-5-chloropentanamide as a colorless crystalline solid, having a melting point of 70°-71° C. and the following physical characteristics: for an additional 16 hours at room temperature washed with water (3×200 ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) dried over anhydrous sodium sulfate The solvent was evaporated off under reduced pressure to yield a crude product The crude product was recrystallized from ethyl acetate-hexane

Conditions: temp:18.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of N-cyclohexyl-5-chloropentanamide (4.36 g, 0.020 mol) in benzene (30 ml) at 0° C. was treated with phosphorous pentachloride (4.4 g, 0.021 mol) in portions over 10 minutes. When the addition was complete the reaction was stirred for an additional 2 hours at 18° C. The solution was then cooled to 0° C. and treated with a solution of hydrazoic acid (0.04 mol) in benzene (50 ml) (prepared according to the method described in Reagents for Organic Synthesis, Volume 1, L. F. Fieser and M. Fieser, John Wiley and Sons (New York: 1967). The resulting solution was stirred at 0° C. for an additional 1.5 hours and at 18° C. for 48 hours and then heated under reflux for an additional 3 hours. The solvent was evaporated off under reduced pressure and the resulting residue was dissolved in ethyl acetate (250 ml). The resulting solution was washed with saturated aqueous sodium hydrogen carbonate (3×100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to yield a crude product. The crude product was purified by recrystallization from ethyl acetate-hexane to yield 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole as a colorless crystalline solid, having a melting point of 50°-51° C. and the following physical characteristics: When the addition The solution was then cooled to 0° C. prepared described in Reagents for Organic Synthesis, Volume 1, L The resulting solution was stirred at 0° C. for an additional 1.5 hours and at 18° C. for 48 hours heated under reflux for an additional 3 hours The solvent was evaporated off under reduced pressure the resulting residue was dissolved in ethyl acetate (250 ml) The resulting solution was washed with saturated aqueous sodium hydrogen carbonate (3×100 ml) dried over anhydrous sodium sulfate filtered concentrated under reduced pressure to yield a crude product The crude product was purified by recrystallization from ethyl acetate-hexane