tert-Butyl N-((2S,1S)-2-hydroxycyclohexyl)carbamate

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

Procedure: (1S,2S)-2-tert-Butoxycarbonylamino-1-cyclohexanol (646 mg) was dissolved in pyridine (4 ml), methane-sulfonyl chloride (378 mg) was added with ice cooling, and the mixture was stirred for 5 hours. After diethyl ether was added to the reaction mixture and washed 5 times with water, the resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (630 mg) as colorless crystals. washed 5 times with water the resultant organic layer was dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure

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

Procedure: To a solution of tert-butyl (1S,2S)-2-hydroxycyclohexylcarbamate (1.30 g, 6.04 mmol), 4-nitrobenzoic acid (1.11 g, 6.64 mmol), triphenylphosphine (1.74 g, 6.64 mmol) in THF (30 mL) was added diethylazo dicarboxylate (1.05 ml, 6.64 mmol) and the resulting solution was stirred at ambient temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was dried and concentrated to give an orange oil that was purified by column chromatography (hexanes/ethyl acetate, 8:1) to give (1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl 4-nitrobenzoate (1.95 g, 89%). washed with brine The organic layer was dried concentrated to give an orange oil that was purified by column chromatography (hexanes/ethyl acetate, 8:1)

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

Procedure: To a solution of tert-butyl (1S,2S)-2-hydroxycyclohexylcarbamate (1.30 g, 6.04 mmol), 4-nitrobenzoic acid (1.11 g, 6.64 mmol), triphenylphosphine (1.74 g, 6.64 mmol) in THF (30 mL) was added diethylazo dicarboxylate (1.05 ml, 6.64 mmol) and the resulting solution was stirred at ambient temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was dried and concentrated to give an orange oil that was purified by column chromatography (hexanes/ethyl acetate, 8:1) to give (1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl 4-nitrobenzoate (1.95 g, 89%). washed with brine The organic layer was dried concentrated to give an orange oil that was purified by column chromatography (hexanes/ethyl acetate, 8:1)

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

Procedure: (1S,2S)-2-tert-Butoxycarbonylamino-1-cyclohexanol (646 mg) was dissolved in pyridine (4 ml), methane-sulfonyl chloride (378 mg) was added with ice cooling, and the mixture was stirred for 5 hours. After diethyl ether was added to the reaction mixture and washed 5 times with water, the resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (630 mg) as colorless crystals. washed 5 times with water the resultant organic layer was dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure

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

Procedure: Triphenylphosphine (14.3 g) was added to a THF (190 ml) solution containing tert-butyl ((1S,2S)-2-hydroxycyclohexyl)carbamate (10.0 g), followed by ice cooling. Diethyl azodicarboxylate (40% in toluene) (24.3 g) and DPPA (15.3 g) were added dropwise to the reaction solution, followed by stirring at room temperature for 1 hour. The reaction solution was left overnight. The solvent was distilled away under reduced pressure. Water was added and then a 20% sodium hydroxide aqueous solution was added. Then, the organic layers were collected. Water (30 ml) was added to the obtained organic layers, followed by heating to 60° C. A THF (40 ml) solution containing triphenylphosphine (14.3 g) was added dropwise, followed by reflux for 2.5 hours. The solvent was distilled away under ordinary pressure. Toluene was added and the pH was adjusted with 3M hydrochloric acid to pH=1 or less. Then, the resulting aqueous layers were collected, ethyl acetate was added, and the pH was adjusted with a 20% sodium hydroxide aqueous solution to pH 12. The organic layers were collected and dried over anhydrous sodium sulfate. Light yellow oily matter of tert-butyl ((1S,2R)-2-aminocyclohexyl)carbamate (5.24 g) was thus obtained. The reaction solution was left overnight The solvent was distilled away under reduced pressure Water was added a 20% sodium hydroxide aqueous solution was added Then, the organic layers were collected Water (30 ml) was added to the obtained organic layers by heating to 60° C A THF (40 ml) solution containing triphenylphosphine (14.3 g) was added dropwise by reflux for 2.5 hours The solvent was distilled away under ordinary pressure Toluene was added Then, the resulting aqueous layers were collected ethyl acetate was added The organic layers were collected dried over anhydrous sodium sulfate

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

Procedure: (1S,2S)-2-tert-Butoxycarbonylamino-1-cyclohexanol (646 mg) was dissolved in pyridine (4 ml), methane-sulfonyl chloride (378 mg) was added with ice cooling, and the mixture was stirred for 5 hours. After diethyl ether was added to the reaction mixture and washed 5 times with water, the resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (630 mg) as colorless crystals. washed 5 times with water the resultant organic layer was dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure

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

Procedure: To a solution of tert-butyl (1S,2S)-2-hydroxycyclohexylcarbamate (1.30 g, 6.04 mmol), 4-nitrobenzoic acid (1.11 g, 6.64 mmol), triphenylphosphine (1.74 g, 6.64 mmol) in THF (30 mL) was added diethylazo dicarboxylate (1.05 ml, 6.64 mmol) and the resulting solution was stirred at ambient temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was dried and concentrated to give an orange oil that was purified by column chromatography (hexanes/ethyl acetate, 8:1) to give (1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl 4-nitrobenzoate (1.95 g, 89%). washed with brine The organic layer was dried concentrated to give an orange oil that was purified by column chromatography (hexanes/ethyl acetate, 8:1)

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

Procedure: (1S,2S)-2-tert-Butoxycarbonylamino-1-cyclohexanol (646 mg) was dissolved in pyridine (4 ml), methane-sulfonyl chloride (378 mg) was added with ice cooling, and the mixture was stirred for 5 hours. After diethyl ether was added to the reaction mixture and washed 5 times with water, the resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (630 mg) as colorless crystals. washed 5 times with water the resultant organic layer was dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure