chloromethyl cyclohexyl carbonate

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

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

Procedure: A solution of 0.78 g of chloromethyl cyclohexyl carbonate and 1.0 g of sodium iodide in 15 ml of acetone is stirred at room temperature for 16 hours and then concentrated under reduced pressure. The residue is extracted with ether and the solvent is distilled off under reduced pressure to give the title compound as pale yellow oil. concentrated under reduced pressure The residue is extracted with ether the solvent is distilled off under reduced pressure

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

Procedure: A solution of 0.78 g of chloromethyl cyclohexyl carbonate and 1.0 g of sodium iodide in 15 ml of acetone is stirred at room temperature for 16 hours and then concentrated under reduced pressure. The residue is extracted with ether and the solvent is distilled off under reduced pressure to give the title compound as pale yellow oil. concentrated under reduced pressure The residue is extracted with ether the solvent is distilled off under reduced pressure

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

Procedure: A solution of 3.0 g of cyclohexanol and 2.4 ml of pyridine in 30 ml of methylene chloride is cooled to -78° C. and, with stirring, 2.4 ml of chloromethyl chloroformate is added dropwise to the solution. After completion of addition, a cold bath is removed. The mixture is stirred at room temperature for 16 hours, washed with three 30-ml portions of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is then distilled off under reduced pressure to give 4.5 g of colorless oil, which is crystallized from ligroine giving the title compound as colorless crystals melting at 36°-37° C. After completion of addition, a cold bath is removed The mixture is stirred at room temperature for 16 hours washed with three 30-ml portions of saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent is then distilled off under reduced pressure

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

Procedure: A solution of 3.0 g of cyclohexanol and 2.4 ml of pyridine in 30 ml of methylene chloride is cooled to -78° C. and, with stirring, 2.4 ml of chloromethyl chloroformate is added dropwise to the solution. After completion of addition, a cold bath is removed. The mixture is stirred at room temperature for 16 hours, washed with three 30-ml portions of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is then distilled off under reduced pressure to give 4.5 g of colorless oil, which is crystallized from ligroine giving the title compound as colorless crystals melting at 36°-37° C. After completion of addition, a cold bath is removed The mixture is stirred at room temperature for 16 hours washed with three 30-ml portions of saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent is then distilled off under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (55% oil) (0.962 g, 22.04 mmol) was suspended in tetrahydrofuran (THF) (200 ml), 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)-butoxy]-1H-quinolin-2-one (8.31 g, 19.17 mmol) was added and the mixture was stirred at 50° C. for 1 hr. The mixture was cooled to 0° C., chloromethyl cyclohexyl carbonate (4.80 g, 24.92 mmol) was added dropwise and the mixture was stirred at room temperature overnight. After cooling to 0° C., excess 2N hydrochloric acid was added to quench the reaction. The precipitated solid was collected by filtration and dried. In addition, the filtrate was extracted with ethyl acetate. The organic layer was concentrated and purified by moderate-pressure silica gel column chromatography (methylene chloride:methanol=100:0 to 20:1). Likewise, the solid was purified by moderate-pressure silica gel column chromatography. Concentration under reduced pressure gave the title compound (yield, 5.04 g, 42%) as a white solid. The mixture was cooled to 0° C. the mixture was stirred at room temperature overnight After cooling to 0° C. to quench the reaction The precipitated solid was collected by filtration dried In addition, the filtrate was extracted with ethyl acetate The organic layer was concentrated purified by moderate-pressure silica gel column chromatography (methylene chloride:methanol=100:0 to 20:1) Likewise, the solid was purified by moderate-pressure silica gel column chromatography Concentration under reduced pressure

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

Procedure: To a solution of (2R)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3S)-2-oxo-3-({[2-(pyrrolidin-1-yl)-1,3-thiazol-5-yl]sulfonyl}amino)pyrrolidin-1-yl]propanoic acid hydrochloride (compound of example 4) (0.5 g, 0.73 mmol) in anhydrous DMF (3 ml) were added potassium carbonate (0.3 g, 2.2 mmol) and chloromethyl cyclohexyl carbonate (0.21 g, 1.1 mmol), followed by potassium iodide (12 mg, 0.07 mmol). The reaction mixture was stirred at room temperature under nitrogen for 12 hours, and then was poured onto cold water, the resulting precipitate was filtered of, washed with water and dried under P2O5. the resulting precipitate was filtered of, washed with water dried under P2O5

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

Procedure: A solution of 0.78 g of chloromethyl cyclohexyl carbonate and 1.0 g of sodium iodide in 15 ml of acetone is stirred at room temperature for 16 hours and then concentrated under reduced pressure. The residue is extracted with ether and the solvent is distilled off under reduced pressure to give the title compound as pale yellow oil. concentrated under reduced pressure The residue is extracted with ether the solvent is distilled off under reduced pressure

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

Procedure: A solution of 3.0 g of cyclohexanol and 2.4 ml of pyridine in 30 ml of methylene chloride is cooled to -78° C. and, with stirring, 2.4 ml of chloromethyl chloroformate is added dropwise to the solution. After completion of addition, a cold bath is removed. The mixture is stirred at room temperature for 16 hours, washed with three 30-ml portions of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is then distilled off under reduced pressure to give 4.5 g of colorless oil, which is crystallized from ligroine giving the title compound as colorless crystals melting at 36°-37° C. After completion of addition, a cold bath is removed The mixture is stirred at room temperature for 16 hours washed with three 30-ml portions of saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent is then distilled off under reduced pressure