methyl (1S,2R)-2-aminocyclohexane-1-carboxylate

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

Procedure: The crude (1S,2R)-2-amino-cyclohexanecarboxylic acid methyl ester (4.97 mmol) was dissolved in methanol (15 mL) at 25° C. and 4-fluorobenzaldehyde (0.533 mL, 4.97 mmol), glacial acetic acid (1 mL) and sodium cyanoborohydride (0.781 g, 12.4 mmol) were added sequentially. The reaction mixture was stirred at 25° C. for 19 h, and then 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-(4-fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester as a yellow oil, which was used directly in the next step without further purification. 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: The crude (1S,2R)-2-amino-cyclohexanecarboxylic acid methyl ester (4.97 mmol) was dissolved in methanol (15 mL) at 25° C. and 4-fluorobenzaldehyde (0.533 mL, 4.97 mmol), glacial acetic acid (1 mL) and sodium cyanoborohydride (0.781 g, 12.4 mmol) were added sequentially. The reaction mixture was stirred at 25° C. for 19 h, and then 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-(4-fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester as a yellow oil, which was used directly in the next step without further purification. 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 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:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1S,2R)-2-aminocyclohexanecarboxylic acid methyl ester (16.2 mmol) and aqueous ammonia (28%, 50 mL) was stirred at room temperature for 24 h. The reaction mixture was concentrated to dryness in vacuo. The residue was suspended in toluene (200 mL) and reconcentrated to afford (1S,2R)-2-aminocyclohexanecarboxylic acid amide as a white solid. The crude product was used in the next step without purification or characterization. The reaction mixture was concentrated to dryness in vacuo

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

Procedure: Thionyl chloride (4.73 mL, 64.8 mmol) was slowly added to a chilled (ice-water bath) suspension of (1S,2R)-2-aminocyclohexanecarboxylic acid (16.2 mmol) in anhydrous methanol (200 mL). After complete addition, the cold bath was removed and the resulting mixture warmed to room temperature. After 24 h, the reaction mixture was evaporated to dryness under a stream of dry nitrogen. The crude product, (1S,2R)-2-aminocyclohexanecarboxylic acid methyl ester, was obtained as a white solid and used in the next step without purification or characterization. a chilled After complete addition the cold bath was removed the reaction mixture was evaporated to dryness under a stream of dry nitrogen

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

Procedure: A mixture of (1S,2R)-2-aminocyclohexanecarboxylic acid methyl ester (16.2 mmol) and aqueous ammonia (28%, 50 mL) was stirred at room temperature for 24 h. The reaction mixture was concentrated to dryness in vacuo. The residue was suspended in toluene (200 mL) and reconcentrated to afford (1S,2R)-2-aminocyclohexanecarboxylic acid amide as a white solid. The crude product was used in the next step without purification or characterization. The reaction mixture was concentrated to dryness in vacuo

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

Procedure: Thionyl chloride (4.73 mL, 64.8 mmol) was slowly added to a chilled (ice-water bath) suspension of (1S,2R)-2-aminocyclohexanecarboxylic acid (16.2 mmol) in anhydrous methanol (200 mL). After complete addition, the cold bath was removed and the resulting mixture warmed to room temperature. After 24 h, the reaction mixture was evaporated to dryness under a stream of dry nitrogen. The crude product, (1S,2R)-2-aminocyclohexanecarboxylic acid methyl ester, was obtained as a white solid and used in the next step without purification or characterization. a chilled After complete addition the cold bath was removed the reaction mixture was evaporated to dryness under a stream of dry nitrogen

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

Procedure: The crude (1S,2R)-2-amino-cyclohexanecarboxylic acid methyl ester (4.97 mmol) was dissolved in methanol (15 mL) at 25° C. and 4-fluorobenzaldehyde (0.533 mL, 4.97 mmol), glacial acetic acid (1 mL) and sodium cyanoborohydride (0.781 g, 12.4 mmol) were added sequentially. The reaction mixture was stirred at 25° C. for 19 h, and then 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-(4-fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester as a yellow oil, which was used directly in the next step without further purification. 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 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:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1S,2R)-2-aminocyclohexanecarboxylic acid methyl ester (16.2 mmol) and aqueous ammonia (28%, 50 mL) was stirred at room temperature for 24 h. The reaction mixture was concentrated to dryness in vacuo. The residue was suspended in toluene (200 mL) and reconcentrated to afford (1S,2R)-2-aminocyclohexanecarboxylic acid amide as a white solid. The crude product was used in the next step without purification or characterization. The reaction mixture was concentrated to dryness in vacuo

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

Procedure: Thionyl chloride (4.73 mL, 64.8 mmol) was slowly added to a chilled (ice-water bath) suspension of (1S,2R)-2-aminocyclohexanecarboxylic acid (16.2 mmol) in anhydrous methanol (200 mL). After complete addition, the cold bath was removed and the resulting mixture warmed to room temperature. After 24 h, the reaction mixture was evaporated to dryness under a stream of dry nitrogen. The crude product, (1S,2R)-2-aminocyclohexanecarboxylic acid methyl ester, was obtained as a white solid and used in the next step without purification or characterization. a chilled After complete addition the cold bath was removed the reaction mixture was evaporated to dryness under a stream of dry nitrogen