methyl (1S,2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 4.0 M solution of hydrochloric acid in 1,4-dioxane (20 mL) was added to a solution of (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid methyl ester (1.28 g, 4.97 mmol) in 1,4-dioxane (15 mL) at 25° C. The reaction mixture was stirred at 25° C. for 2 h, then toluene (40 mL) was added and the volatiles were removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo to afford the crude product, (1S,2R)-2-amino-cyclohexanecarboxylic acid methyl ester as a yellow oil, which was used directly in the next step without further purification. the volatiles were removed in vacuo The residue was partitioned between saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL) The combined organic layers were dried over sodium sulfate decanted were concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether (5.0 mL, 10.0 mmol) was added over 10 min to a solution of (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid (0.994 g, 4.09 mmol; purchased from NeoMPS) in a 1:1 mixture of benzene and methanol (50 mL) at 25° C. The resulting mixture was stirred at 25° C. for 30 min, and then was partitioned between half-saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo to afford the desired product, (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid methyl ester (1.00 g, 3.89 mmol, 95%), as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.44 (9H, s), 1.58-1.68 (3H, m), 1.72-1.81 (2H, m), 1.98-2.05 (2H, m), 2.77-2.80 (1H, m), 3.69 (3H, s), 3.82-3.90 (1H, m), 5.29-5.31 (1H, m). LC-MS (ESI) calcd for C13H23NO4 257.16, found 258.2 [M+H+]. was partitioned between half-saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL) The combined organic layers were dried over sodium sulfate decanted were concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether (5.0 mL, 10.0 mmol) was added over 10 min to a solution of (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid (0.994 g, 4.09 mmol; purchased from NeoMPS) in a 1:1 mixture of benzene and methanol (50 mL) at 25° C. The resulting mixture was stirred at 25° C. for 30 min, and then was partitioned between half-saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo to afford the desired product, (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid methyl ester (1.00 g, 3.89 mmol, 95%), as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.44 (9H, s), 1.58-1.68 (3H, m), 1.72-1.81 (2H, m), 1.98-2.05 (2H, m), 2.77-2.80 (1H, m), 3.69 (3H, s), 3.82-3.90 (1H, m), 5.29-5.31 (1H, m). LC-MS (ESI) calcd for C13H23NO4 257.16, found 258.2 [M+H+]. was partitioned between half-saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL) The combined organic layers were dried over sodium sulfate decanted were concentrated in vacuo

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

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

Procedure: Sodium metal (0.14 g, 6.1 mmol) was placed into a flame dried flask under nitrogen atmosphere and cooled to 0° C. 10 mL of freshly distilled methanol was added and the mixture stirred until all the sodium dissolved. An amount of 25 (2.00 g, 7.7 mmol) was dissolved in 10 mL of freshly distilled methanol and transferred to NaOMe solution via cannula. The solution was refluxed under nitrogen for 5.5 h, cooled to rt and acidified with 0.5 M aqueous 0.5 M ammonium chloride (18 mL, 9 mmol). The methanol was removed under reduced pressure, and the resulting solid collected by filtration to yield 1.27 g of desired product. dried flask under nitrogen atmosphere 10 mL of freshly distilled methanol was added dissolved The solution was refluxed under nitrogen for 5.5 h cooled to rt The methanol was removed under reduced pressure the resulting solid collected by filtration

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 4.0 M solution of hydrochloric acid in 1,4-dioxane (20 mL) was added to a solution of (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid methyl ester (1.28 g, 4.97 mmol) in 1,4-dioxane (15 mL) at 25° C. The reaction mixture was stirred at 25° C. for 2 h, then toluene (40 mL) was added and the volatiles were removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo to afford the crude product, (1S,2R)-2-amino-cyclohexanecarboxylic acid methyl ester as a yellow oil, which was used directly in the next step without further purification. the volatiles were removed in vacuo The residue was partitioned between saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL) The combined organic layers were dried over sodium sulfate decanted were concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether (5.0 mL, 10.0 mmol) was added over 10 min to a solution of (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid (0.994 g, 4.09 mmol; purchased from NeoMPS) in a 1:1 mixture of benzene and methanol (50 mL) at 25° C. The resulting mixture was stirred at 25° C. for 30 min, and then was partitioned between half-saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo to afford the desired product, (1S,2R)-2-tert-butoxycarbonylamino-1-cyclohexanecarboxylic acid methyl ester (1.00 g, 3.89 mmol, 95%), as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.44 (9H, s), 1.58-1.68 (3H, m), 1.72-1.81 (2H, m), 1.98-2.05 (2H, m), 2.77-2.80 (1H, m), 3.69 (3H, s), 3.82-3.90 (1H, m), 5.29-5.31 (1H, m). LC-MS (ESI) calcd for C13H23NO4 257.16, found 258.2 [M+H+]. was partitioned between half-saturated sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL) The combined organic layers were dried over sodium sulfate decanted were concentrated in vacuo