tert-butyl N-[3-(hydroxymethyl)cyclohexyl]carbamate

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

Procedure: To a solution of tert-butyl [3-(hydroxymethyl)cyclohexyl]carbamate (0.51 g, 2.2 mmol) in methylene chloride (10 mL) at 0° C. was added Dess-Martin periodinane (1.1 g, 2.7 mmol). The mixture was stirred at room temperature for 2 h. The reaction was quenched with aq. 1N NaOH solution and extracted with methylene chloride. The combined organic layers were washed with water and then brine, dried over MgSO4, concentrated, and then purified on silica gel column (eluting with 20-50% EtOAc in hexanes) to give the desired product (0.3 g, 59%). LCMS calculated for C12H21NO3Na (M+Na)+: m/z=250.2. Found: 250.1. The reaction was quenched with aq. 1N NaOH solution extracted with methylene chloride The combined organic layers were washed with water brine, dried over MgSO4 concentrated purified on silica gel column (eluting with 20-50% EtOAc in hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (from Alfa Aesar, 3.3 g, 14 mmol) and triethylamine (3.8 mL, 27 mmol) in tetrahydrofuran (40 mL) at 0° C. was added dropwise ethyl chloroformate (1.9 mL, 20 mmol). The mixture was stirred at 0° C. for 10 min and then at room temperature for 20 min. The mixture was filtered to remove the white solid and then cooled to 0° C. A mixture of sodium tetrahydroborate (1.0 g, 27 mmol) and methanol (1 mL) was added slowly. The mixture was stirred at room temperature for 1 h. The mixture was quenched with 1N aq. HCl solution and extracted with EtOAc. The extracts were concentrated and purified on silica gel column (eluting with 75% EtOAc in hexanes) to give the desired product (2.88 g, 92%). LCMS calculated for C13H23NO3Na (M+Na)+: m/z=252.2. Found: 252.1. at room temperature for 20 min The mixture was filtered to remove the white solid cooled to 0° C was added slowly The mixture was stirred at room temperature for 1 h The mixture was quenched with 1N aq. HCl solution extracted with EtOAc The extracts were concentrated purified on silica gel column (eluting with 75% EtOAc in hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (from Alfa Aesar, 3.3 g, 14 mmol) and triethylamine (3.8 mL, 27 mmol) in tetrahydrofuran (40 mL) at 0° C. was added dropwise ethyl chloroformate (1.9 mL, 20 mmol). The mixture was stirred at 0° C. for 10 min and then at room temperature for 20 min. The mixture was filtered to remove the white solid and then cooled to 0° C. A mixture of sodium tetrahydroborate (1.0 g, 27 mmol) and methanol (1 mL) was added slowly. The mixture was stirred at room temperature for 1 h. The mixture was quenched with 1N aq. HCl solution and extracted with EtOAc. The extracts were concentrated and purified on silica gel column (eluting with 75% EtOAc in hexanes) to give the desired product (2.88 g, 92%). LCMS calculated for C13H23NO3Na (M+Na)+: m/z=252.2. Found: 252.1. at room temperature for 20 min The mixture was filtered to remove the white solid cooled to 0° C was added slowly The mixture was stirred at room temperature for 1 h The mixture was quenched with 1N aq. HCl solution extracted with EtOAc The extracts were concentrated purified on silica gel column (eluting with 75% EtOAc in hexanes)

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

Procedure: A mixture of tert-butyl 3-(hydroxymethyl)cyclohexylcarbamate (7.9 mmol), methanesulfonyl chloride (23.7 mmol) and triethylamine (119 mmol) in DCM (100 ml) was stirred at rt overnight. The reaction was quenched with water (50 mL) and extracted with ethyl acetate (3×100 mL). The extracts were combined, dried using anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was progressed to the next step without purification. The reaction was quenched with water (50 mL) extracted with ethyl acetate (3×100 mL) dried filtered concentrated in vacuo The crude product was progressed to the next step without purification

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

Procedure: To a solution of methyl 3-(tert-butoxycarbonylamino)cyclohexanecarboxylate (9 mmol) in THF/MeOH/CH2Cl2 (36 ml, 10:1:1) was added NaBH4 (22.5 mmol) and stirred at rt overnight. The reaction was quenched with water and extracted with CH2Cl2 (3×10 mL). The extracts were combined and dried using anhydrous sodium sulfate. The product was purified using Biotage. The reaction was quenched with water extracted with CH2Cl2 (3×10 mL) dried The product was purified

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

Procedure: To a solution of methyl 3-(tert-butoxycarbonylamino)cyclohexanecarboxylate (9 mmol) in THF/MeOH/CH2Cl2 (36 ml, 10:1:1) was added NaBH4 (22.5 mmol) and stirred at rt overnight. The reaction was quenched with water and extracted with CH2Cl2 (3×10 mL). The extracts were combined and dried using anhydrous sodium sulfate. The product was purified using Biotage. The reaction was quenched with water extracted with CH2Cl2 (3×10 mL) dried The product was purified

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

Procedure: To a solution of tert-butyl 3-(hydroxymethyl)cyclohexylcarbamate (1.4 g, 6.11 mmol) in dimethylsulfoxide (10 mL) was added triethylamine (1.853 g, 18.32 mmol) followed by the pyridine-sulfur trioxide (2.92 g, 18.32 mmol) in 5 mL of dimethylsulfoxide, and the mixture was stirred at room temperature for 1 hour. The mixture was quenched with ice water and extracted into ethyl acetate (30 mL×2). The organic layer was washed with water and brine solution (25 mL each), dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the title compound. The mixture was quenched with ice water extracted into ethyl acetate (30 mL×2) The organic layer was washed with water and brine solution (25 mL each) dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: To a solution of tert-butyl [3-(hydroxymethyl)cyclohexyl]carbamate (0.51 g, 2.2 mmol) in methylene chloride (10 mL) at 0° C. was added Dess-Martin periodinane (1.1 g, 2.7 mmol). The mixture was stirred at room temperature for 2 h. The reaction was quenched with aq. 1N NaOH solution and extracted with methylene chloride. The combined organic layers were washed with water and then brine, dried over MgSO4, concentrated, and then purified on silica gel column (eluting with 20-50% EtOAc in hexanes) to give the desired product (0.3 g, 59%). LCMS calculated for C12H21NO3Na (M+Na)+: m/z=250.2. Found: 250.1. The reaction was quenched with aq. 1N NaOH solution extracted with methylene chloride The combined organic layers were washed with water brine, dried over MgSO4 concentrated purified on silica gel column (eluting with 20-50% EtOAc in hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (from Alfa Aesar, 3.3 g, 14 mmol) and triethylamine (3.8 mL, 27 mmol) in tetrahydrofuran (40 mL) at 0° C. was added dropwise ethyl chloroformate (1.9 mL, 20 mmol). The mixture was stirred at 0° C. for 10 min and then at room temperature for 20 min. The mixture was filtered to remove the white solid and then cooled to 0° C. A mixture of sodium tetrahydroborate (1.0 g, 27 mmol) and methanol (1 mL) was added slowly. The mixture was stirred at room temperature for 1 h. The mixture was quenched with 1N aq. HCl solution and extracted with EtOAc. The extracts were concentrated and purified on silica gel column (eluting with 75% EtOAc in hexanes) to give the desired product (2.88 g, 92%). LCMS calculated for C13H23NO3Na (M+Na)+: m/z=252.2. Found: 252.1. at room temperature for 20 min The mixture was filtered to remove the white solid cooled to 0° C was added slowly The mixture was stirred at room temperature for 1 h The mixture was quenched with 1N aq. HCl solution extracted with EtOAc The extracts were concentrated purified on silica gel column (eluting with 75% EtOAc in hexanes)

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

Procedure: A mixture of tert-butyl 3-(hydroxymethyl)cyclohexylcarbamate (7.9 mmol), methanesulfonyl chloride (23.7 mmol) and triethylamine (119 mmol) in DCM (100 ml) was stirred at rt overnight. The reaction was quenched with water (50 mL) and extracted with ethyl acetate (3×100 mL). The extracts were combined, dried using anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was progressed to the next step without purification. The reaction was quenched with water (50 mL) extracted with ethyl acetate (3×100 mL) dried filtered concentrated in vacuo The crude product was progressed to the next step without purification

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

Procedure: To a solution of methyl 3-(tert-butoxycarbonylamino)cyclohexanecarboxylate (9 mmol) in THF/MeOH/CH2Cl2 (36 ml, 10:1:1) was added NaBH4 (22.5 mmol) and stirred at rt overnight. The reaction was quenched with water and extracted with CH2Cl2 (3×10 mL). The extracts were combined and dried using anhydrous sodium sulfate. The product was purified using Biotage. The reaction was quenched with water extracted with CH2Cl2 (3×10 mL) dried The product was purified