tert-butyl N-(3-oxocyclohexyl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction mixture of tert-butyl 3-oxocyclohexylcarbamate (4 mmol, 852 mg) and benzylamine (4 mmol, 436 μL) in refluxing toluene (25 mL) in a Dean-Stark apparatus was stirred for overnight. The product, tert-butyl 3-(benzylimino)cyclohexylcarbamate, was obtained after evaporation of solvent.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Me3SOI (56.2 mmol) in DMSO (80 ml) was added NaH (51.5 mmol) and stirred at room temperature for 2 h until the solution become clear. The resulting solution was added tert-butyl 3-oxocyclohexylcarbamate (23.4 mmol) and stirred at rt overnight. The reaction was quenched with water and extracted with hexane. The extracts were combined and dried using anhydrous sodium sulfate. The product was purified using Biotage. The final products, isomer 1 and isomer 2, were well separated on silicon column with 15%-20% ethyl acetate in hexane. Each single diastereomer was used for the next step. stirred at rt overnight The reaction was quenched with water extracted with hexane dried The product was purified The final products, isomer 1 and isomer 2, were well separated on silicon column with 15%-20% ethyl acetate in hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Me3SOI (56.2 mmol) in DMSO (80 ml) was added NaH (51.5 mmol) and stirred at room temperature for 2 h until the solution become clear. The resulting solution was added tert-butyl 3-oxocyclohexylcarbamate (23.4 mmol) and stirred at rt overnight. The reaction was quenched with water and extracted with hexane. The extracts were combined and dried using anhydrous sodium sulfate. The product was purified using Biotage. The final products, isomer 1 and isomer 2, were well separated on silicon column with 15%-20% ethyl acetate in hexane. Each single diastereomer was used for the next step. stirred at rt overnight The reaction was quenched with water extracted with hexane dried The product was purified The final products, isomer 1 and isomer 2, were well separated on silicon column with 15%-20% ethyl acetate in hexane

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-phenyl-1,3-dithiane (12 mmol, 2.35 g) in THF (15 mL) at −78° C. was added a solution of lithium diisopropylamide in THF/heptane/ethylbenzene (12 mmol, 1.8 M, 6.7 mL) under argon. The reaction mixture was warmed up to −20° C. and stirred for 30 minutes at −20° C. The reaction mixture was cooled down to −78° C. tert-Butyl 3-oxocyclohexylcarbamate (5 mmol, 1.065 g) in THF was added. The reaction mixture was allowed to warm up to room temperature and stirred for overnight. Acetic anhydride (20 mmol, 1.9 mL) was added. The reaction mixture was stirred at room temperature for 4 hours. Water was added. The organics were extracted with EtOAc. 3-(tert-Butoxycarbonylamino)-1-(2-phenyl-1,3-dithiaN-2-yl)cyclohexyl acetate was obtained after purification by silica gel column chromatography. was added to warm up to room temperature stirred for overnight The reaction mixture was stirred at room temperature for 4 hours The organics were extracted with EtOAc

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-phenyl-1,3-dithiane (12 mmol, 2.35 g) in THF (15 mL) at 78° C. was added a solution of lithium diisopropylamide in THF/heptane/ethylbenzene (12 mmol, 1.8 M, 6.7 mL) under argon. The reaction mixture was warmed up to −20° C. and stirred for 30 minutes at −20° C. The reaction mixture was cooled down to −78° C. tert-Butyl 3-oxocyclohexylcarbamate (5 mmol, 1.065 g) in THF was added. The reaction mixture was allowed to warm up to room temperature and stirred for overnight. Acetic anhydride (20 mmol, 1.9 mL) was added. The reaction mixture was stirred at room temperature for 4 hours. Water was added. The organics were extracted with EtOAc. 3-(tert-Butoxycarbonylamino)-1-(2-phenyl-1,3-dithiaN-2-yl)cyclohexyl acetate was obtained after purification by silica gel column chromatography. was added to warm up to room temperature stirred for overnight The reaction mixture was stirred at room temperature for 4 hours The organics were extracted with EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the mixture of tert-butyl 3-oxocyclohexylcarbamate (5 mmol, 1.065 g), 3-fluorophenol (5 mmol, 560 mg) and NaOH (25 mmol, 1 g) in THF at 0° C. was added bromoform (25 mmol, 2.2 mL) dropwise. The reaction mixture was allowed to warm to room temperature and stirred for overnight. The reaction mixture was concentrated. The product, 3-(tert-butoxycarbonylamino)-1-(3-fluorophenoxy)cyclohexanecarboxylic acid, was obtained (60 mg, 3% yield) after purification by reverse phase HPLC. The reaction mixture was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl 3-oxocyclohexylcarbamate (2 mmol, 426 mg) in ethyl ether (10 mL) was added a solution of (2-fluorobenzyl)magnesium bromide in ether (5 mmol, 0.25 M, 20 mL) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for overnight. The reaction mixture was added to the NH4Cl aqueous solution. The organics were extracted with EtOAc. The EtOAc solution was concentrated. The product, tert-butyl 3-(2-fluorobenzyl)-3-hydroxycyclohexylcarbamate was purified by column chromatography on silica gel. The organics were extracted with EtOAc The EtOAc solution was concentrated The product, tert-butyl 3-(2-fluorobenzyl)-3-hydroxycyclohexylcarbamate was purified by column chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl 3-oxocyclohexylcarbamate (2 mmol, 426 mg) in ethyl ether (10 mL) was added a solution of (2-fluorobenzyl)magnesium bromide in ether (5 mmol, 0.25 M, 20 mL) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for overnight. The reaction mixture was added to the NH4Cl aqueous solution. The organics were extracted with EtOAc. The EtOAc solution was concentrated. The product, tert-butyl 3-(2-fluorobenzyl)-3-hydroxycyclohexylcarbamate was purified by column chromatography on silica gel. The organics were extracted with EtOAc The EtOAc solution was concentrated The product, tert-butyl 3-(2-fluorobenzyl)-3-hydroxycyclohexylcarbamate was purified by column chromatography on silica gel

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction mixture of tert-butyl 3-oxocyclohexylcarbamate (4 mmol, 852 mg) and benzylamine (4 mmol, 436 μL) in refluxing toluene (25 mL) in a Dean-Stark apparatus was stirred for overnight. The product, tert-butyl 3-(benzylimino)cyclohexylcarbamate, was obtained after evaporation of solvent.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Me3SOI (56.2 mmol) in DMSO (80 ml) was added NaH (51.5 mmol) and stirred at room temperature for 2 h until the solution become clear. The resulting solution was added tert-butyl 3-oxocyclohexylcarbamate (23.4 mmol) and stirred at rt overnight. The reaction was quenched with water and extracted with hexane. The extracts were combined and dried using anhydrous sodium sulfate. The product was purified using Biotage. The final products, isomer 1 and isomer 2, were well separated on silicon column with 15%-20% ethyl acetate in hexane. Each single diastereomer was used for the next step. stirred at rt overnight The reaction was quenched with water extracted with hexane dried The product was purified The final products, isomer 1 and isomer 2, were well separated on silicon column with 15%-20% ethyl acetate in hexane