tert-butyl N-(2-aminocyclopentyl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) (500 mg, 2.497 mmol) in 10 ml methanol was added acetic acid (0.714 ml, 12.49 mmol) and cyclopentanone (0.665 ml, 7.491 mmol). The mixture was heated in a 50° C. oil bath for 1.5 hour. The solution was cooled to room temperature and sodium cyanoborohydride (370 mg, 5.0 mmol) was added portionwise. The mixture was heated in a 50° C. oil bath for 2.5 hours. The solution was cooled in an ice bath and quenched by dropwise addition of 6 ml 2N NaOH. The methanol was removed in vacuo. The aqueous layer was diluted with water and extracted 3 times with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified on silica gel (eluent: heptane/ethyl acetate 0 to 100%) to provide 0.39 g (58%) of the title compound as a light brown solid. MS (m/e): 269.3 (M+H). The solution was cooled to room temperature The mixture was heated in a 50° C. oil bath for 2.5 hours The solution was cooled in an ice bath quenched by dropwise addition of 6 ml 2N NaOH The methanol was removed in vacuo The aqueous layer was diluted with water extracted 3 times with ethyl acetate The combined extracts were dried over Na2SO4 filtered concentrated in vacuo The crude oil was purified on silica gel (eluent: heptane/ethyl acetate 0 to 100%)

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

Procedure: The title compound, light yellow solid, MS: m/e=401.4 [(M+H)+], was prepared in accordance with the general method of intermediate N from [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) and 2-ethyl-4-(trifluoromethyl)-benzoic acid (CAS 854531-63-8).

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

Procedure: The title compound, brown oil, MS: m/e=255.3 [(M+H)+], was prepared in accordance with the general method of intermediate E from [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) and 1,4-dibromobutane.

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

Procedure: The title compound, brown oil, MS: m/e=255.3 [(M+H)+], was prepared in accordance with the general method of intermediate E from [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) and 1,4-dibromobutane.

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

Procedure: 2-Methoxy-6-methylsulfanyl-4-trifluoromethyl-benzoic acid (intermediate A, 1.1 g, 4.1 mmol) was dissolved in 40 mL dimethylformamide. N,N-Diisopropyl ethyl amine (763 mg, 5.9 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.57 g, 4.1 mmol) were added. After 5 minutes of stirring at room temperature [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) (993 mg, 5 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane ethyl acetate 100:0→1:1) yielded the title compound as a white solid (1.8 g, 100%), MS: m/e=449.2 [(M+H)+]. was added The solvent was evaporated off ethyl acetate and was extracted three times with ethyl acetate The combined organic phases were dried on sodium sulfate filtered evaporated Purification of the residue by flash chromatography on silica gel (heptane ethyl acetate 100:0→1:1)

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

Procedure: 2-Methoxy-6-methylsulfanyl-4-trifluoromethyl-benzoic acid (intermediate A, 1.1 g, 4.1 mmol) was dissolved in 40 mL dimethylformamide. N,N-Diisopropyl ethyl amine (763 mg, 5.9 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.57 g, 4.1 mmol) were added. After 5 minutes of stirring at room temperature [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) (993 mg, 5 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane ethyl acetate 100:0→1:1) yielded the title compound as a white solid (1.8 g, 100%), MS: m/e=449.2 [(M+H)+]. was added The solvent was evaporated off ethyl acetate and was extracted three times with ethyl acetate The combined organic phases were dried on sodium sulfate filtered evaporated Purification of the residue by flash chromatography on silica gel (heptane ethyl acetate 100:0→1:1)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of [(1RS, 2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) (500 mg, 2.497 mmol) in 10 ml methanol was added acetic acid (0.714 ml, 12.49 mmol) and cyclopentanone (0.665 ml, 7.491 mmol). The mixture was heated in a 50° C. oil bath for 1.5 hour. The solution was cooled to room temperature and sodium cyanoborohydride (370 mg, 5.0 mmol) was added portionwise. The mixture was heated in a 50° C. oil bath for 2.5 hours. The solution was cooled in an ice bath and quenched by dropwise addition of 6 ml 2N NaOH. The methanol was removed in vacuo. The aqueous layer was diluted with water and extracted 3 times with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified on silica gel (eluent: heptane/ethyl acetate 0 to 100%) to provide 0.39 g (58%) of the title compound as a light brown solid. MS (m/e): 269.3 (M+H). The solution was cooled to room temperature The mixture was heated in a 50° C. oil bath for 2.5 hours The solution was cooled in an ice bath quenched by dropwise addition of 6 ml 2N NaOH The methanol was removed in vacuo The aqueous layer was diluted with water extracted 3 times with ethyl acetate The combined extracts were dried over Na2SO4 filtered concentrated in vacuo The crude oil was purified on silica gel (eluent: heptane/ethyl acetate 0 to 100%)

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

Procedure: The title compound, light yellow solid, MS: m/e=401.4 [(M+H)+], was prepared in accordance with the general method of intermediate N from [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) and 2-ethyl-4-(trifluoromethyl)-benzoic acid (CAS 854531-63-8).

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

Procedure: The title compound, brown oil, MS: m/e=255.3 [(M+H)+], was prepared in accordance with the general method of intermediate E from [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) and 1,4-dibromobutane.

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

Procedure: 2-Methoxy-6-methylsulfanyl-4-trifluoromethyl-benzoic acid (intermediate A, 1.1 g, 4.1 mmol) was dissolved in 40 mL dimethylformamide. N,N-Diisopropyl ethyl amine (763 mg, 5.9 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.57 g, 4.1 mmol) were added. After 5 minutes of stirring at room temperature [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) (993 mg, 5 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane ethyl acetate 100:0->1:1) yielded the title compound as a white solid (1.8 g, 100%), MS: m/e=449.2 [(M+H)+]. was added The solvent was evaporated off ethyl acetate and was extracted three times with ethyl acetate The combined organic phases were dried on sodium sulfate filtered evaporated Purification of the residue by flash chromatography on silica gel (heptane ethyl acetate 100:0->1:1)