benzyl cyclohexanecarboxylate

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 benzyl cyclohexanecarboxylate (1.44 g) in tetrahydrofuran (40 mL) was added a 1M solution of lithium hexamethyldisilazane in tetrahydrofuran (9.9 mL) under ice cooling. The solution was stirred at room temperature for 1 hour under ice cooling, to which hexamethylphosporamide (2.3 mL) was added. The solution was then stirred for additional 10 minutes. To the solution was added allyl bromide (1.4 mL). The solution was stirred under ice cooling for 1 hour, to which allyl bromide (1.4 mL) was further added. The solution was stirred at room temperature for 18 hours. Water and 3N hydrochloric acid were added to the solution, and it was extracted with diethyl ether. The organic layer was washed in turn with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The solution was dried over anhydrous magnesium sulfate, and then, concentrated under reduced pressure. The resulting residue was purified by chromatography (silica gel, hexane:ethyl acetate=99:1) to give the title compound (550 mg). This product was subjected to the subsequent step without further purification. was added The solution was then stirred for additional 10 minutes was further added The solution was stirred at room temperature for 18 hours was extracted with diethyl ether The organic layer was washed in turn with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution The solution was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by chromatography (silica gel, hexane:ethyl acetate=99:1)

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

Procedure: To a solution of benzyl cyclohexanecarboxylate (1.44 g) in tetrahydrofuran (40 mL) was added a 1M solution of lithium hexamethyldisilazane in tetrahydrofuran (9.9 mL) under ice cooling. The solution was stirred at room temperature for 1 hour under ice cooling, to which hexamethylphosporamide (2.3 mL) was added. The solution was then stirred for additional 10 minutes. To the solution was added allyl bromide (1.4 mL). The solution was stirred under ice cooling for 1 hour, to which allyl bromide (1.4 mL) was further added. The solution was stirred at room temperature for 18 hours. Water and 3N hydrochloric acid were added to the solution, and it was extracted with diethyl ether. The organic layer was washed in turn with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The solution was dried over anhydrous magnesium sulfate, and then, concentrated under reduced pressure. The resulting residue was purified by chromatography (silica gel, hexane:ethyl acetate=99:1) to give the title compound (550 mg). This product was subjected to the subsequent step without further purification. was added The solution was then stirred for additional 10 minutes was further added The solution was stirred at room temperature for 18 hours was extracted with diethyl ether The organic layer was washed in turn with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution The solution was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by chromatography (silica gel, hexane:ethyl acetate=99:1)

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

Procedure: To a solution of cyclohexanecarboxylic acid (2.56 g) in dichloromethane (50 ml) and N,N-dimethylformamide (0.5 mL) was added oxalyl chloride (1.92 mL) under ice cooling. The solution was stirred at room temperature for 1 hour and then concentrated under reduced pressure. A solution of the resulting residue in dichloromethane (30 mL) was added to a solution of benzyl alcohol (2.4 g) and triethylamine (8.4 mL) in dichloromethane (30 mL) under ice cooling. The solution was stirred under ice cooling for 1 hour, and then it was washed in turn with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The solution was dried over anhydrous magnesium sulfate, and then, concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, hexane:ethyl acetate=9:1) to give the title compound (3.44 g). concentrated under reduced pressure A solution of the resulting residue in dichloromethane (30 mL) was added to a solution of benzyl alcohol (2.4 g) and triethylamine (8.4 mL) in dichloromethane (30 mL) under ice cooling The solution was stirred under ice cooling for 1 hour it was washed in turn with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution The solution was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by column chromatography (silica gel, hexane:ethyl acetate=9:1)

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

Procedure: 0.7 ml of 2N aqueous sodium hydroxide solution was added to a solution of 100 mg (0.25 mmol) of 1-[[[4-(dimethylamino)methyl]phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl ester in 1 ml of tetrahydrofuran, and the mixture was heated under reflux overnight. After the mixture was neutralized by concentrated hydrochloric acid, the reaction solution was distilled off under reduced pressure. 3 ml of methylene chloride, 126 mg (1.25 mmol) of triethylamine and 96 mg (0.5 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride were added to the residue, and the mixture was stirred for 1 hour. The reaction solution was distilled off under reduced pressure, a saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 52 mg (68%) of the title compound. the mixture was heated under reflux overnight the reaction solution was distilled off under reduced pressure The reaction solution was distilled off under reduced pressure a saturated aqueous sodium bicarbonate solution was added the mixture was extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium bicarbonate solution dried with anhydrous sodium sulfate The solvent was distilled off under reduced pressure