tert-butyl N-(3-hydroxycyclohexyl)carbamate

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of tert-butyl 3-hydroxycyclohexylcarbamate (4 mmol, 861 mg), 1-fluoro-2-iodobenzene (5 mmol, 585 4), copper iodide (0.4 mmol, 76 mg), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.8 mmol, 190 mg) and cesium carbonate (10 mmol, 3.26 g) in toluene (5 mL) was stirred at 110° C. for overnight under argon. The reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated. The mixture was purified by silica gel column chromatography. The product, tert-butyl 3-(2-fluorophenoxy)cyclohexylcarbamate, was eluted off the column using 15% EtOAc in Hexane. The reaction mixture was cooled to room temperature filtered through celite The filtrate was concentrated The mixture was purified by silica gel column chromatography The product, tert-butyl 3-(2-fluorophenoxy)cyclohexylcarbamate, was eluted off the column

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of tert-butyl 3-hydroxycyclohexylcarbamate (4 mmol, 861 mg), 1-fluoro-2-iodobenzene (5 mmol, 585 4), copper iodide (0.4 mmol, 76 mg), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.8 mmol, 190 mg) and cesium carbonate (10 mmol, 3.26 g) in toluene (5 mL) was stirred at 110° C. for overnight under argon. The reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated. The mixture was purified by silica gel column chromatography. The product, tert-butyl 3-(2-fluorophenoxy)cyclohexylcarbamate, was eluted off the column using 15% EtOAc in Hexane. The reaction mixture was cooled to room temperature filtered through celite The filtrate was concentrated The mixture was purified by silica gel column chromatography The product, tert-butyl 3-(2-fluorophenoxy)cyclohexylcarbamate, was eluted off the column

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

Procedure: To a solution of crude tert-butyl (3-hydroxycyclohexyl)carbamate (4.0 g, crude) in DCM (40 mL) was added TFA (20 mL) under cooling in an ice bath. The resulting reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated to give a crude product (3.0 g, crude), which was used in the next step without further purification. MS (ESI) m/z 130.1 [M+H]+. under cooling in an ice bath The resulting reaction mixture The mixture was concentrated

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed suspension of tert-butyl(3-oxocyclohexyl)carbamate (4.0 g, 18.78 mmol) in dry THF 200 mL) was added a solution of methyllithium in THF (3M, 25.0 mL, 75 mmol) at −75° C. The resulting reaction mixture was stirred at −75° C. for 1 h. A solution of methyllithium in THF (3M, 25.0 mL, 75 mmol) was added at −75° C. and the mixture was stirred for 1 h. Aqueous ammonia chloride solution was added dropwise to quench the reaction. The resulting reaction mixture was continued to stir at room temperature for 2 h. The reaction mixture was extracted with ethyl acetate (150 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford the crude product (4.0 g, crude), which was used directly in the next step without purification. MS (ESI) m/z 230.1 [M+H]+. The resulting reaction mixture the mixture was stirred for 1 h to quench the reaction The resulting reaction mixture to stir at room temperature for 2 h The reaction mixture was extracted with ethyl acetate (150 mL×3) The combined organic layers were washed with brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: To a solution of tert-butyl (3-hydroxycyclohexyl)carbamate (4.40 g, 20.46 mmol) in DCM (250 mL) was added Dess-Martin periodinane (13.0 g, 30.70 mmol) in portions under cooling in an ice bath. The mixture was stirred at room temperature for 2 h. The reaction was diluted with DCM and washed with aqueous sodium carbonate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated. The crude compound was purified by silica gel column chromatography (40% ethyl acetate in petroleum ether) to afford the title compound (4.0 g, 18.78 mmol, 91% yield). MS (ESI) m/z 214.1 [M+H]+. under cooling in an ice bath washed with aqueous sodium carbonate The separated organic layer was dried over anhydrous sodium sulfate concentrated The crude compound was purified by silica gel column chromatography (40% ethyl acetate in petroleum ether)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of tert-butyl 3-hydroxycyclohexylcarbamate (4 mmol, 861 mg), 1-fluoro-2-iodobenzene (5 mmol, 585 4), copper iodide (0.4 mmol, 76 mg), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.8 mmol, 190 mg) and cesium carbonate (10 mmol, 3.26 g) in toluene (5 mL) was stirred at 110° C. for overnight under argon. The reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated. The mixture was purified by silica gel column chromatography. The product, tert-butyl 3-(2-fluorophenoxy)cyclohexylcarbamate, was eluted off the column using 15% EtOAc in Hexane. The reaction mixture was cooled to room temperature filtered through celite The filtrate was concentrated The mixture was purified by silica gel column chromatography The product, tert-butyl 3-(2-fluorophenoxy)cyclohexylcarbamate, was eluted off the column