(1S,2S)-反式-N-BOC-2-氨基环戊醇

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1S,2S)-trans-N-boc-2-aminocyclopentanol was dissolved in 50 ml THF and cooled to 10° C. To the reaction mixture were added 32.2 ml LiHMDS 1M in THF. After 1 hour 2.72 ml 2,4-difluoronitrobenzol were added and the mixture was stirred at rt overnight. Then the mixture was poured in water and extracted with ethylacetate. The organic layer was washed with water, dried and concentrated in vacuo. extracted with ethylacetate The organic layer was washed with water dried concentrated in vacuo

反应条件: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of oxalyl chloride (6.47 mL, 74.5 mmol) in THF (166 mL) is cooled to −72° C. under nitrogen and treated dropwise with DMSO (10.59 mL, 149.1 mmol). The mixture is stirred for 5 min, whereupon tert-butyl (1S,2S)-2-hydroxycyclopentylcarbamate (10.0 g, 49.7 mmol) is added. Stirring is continued at −75° C. for 45 min. Triethylamine (37.4 mL, 268.3 mmol) is added slowly keeping the temperature below −68° C. After the addition is complete the reaction is allowed to warm slowly to room temperature overnight. The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) completed earlier. Water (100 mL) is added and the reaction is concentrated in vacuo to remove THF. The mixture is extracted with EtOAc (3×150 mL). The combined organic portions are dried over sodium sulfate, filtered, and concentrated to give 12.41 g of crude product as a yellow oil. The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes) to give the title compound (9.17 g, 93%). 1H-NMR (400 MHz, CDCl3) δ 5.04-5.02 (m, 1H), 3.98-3.96 (m, 1H), 2.65-2.63 (m, 1H), 2.44-2.39 (m, 1H), 2.21-2.11 (m, 1H), 2.04 (s, 1H), 1.89-1.85 (m, 1H), 1.66-1.59 (m, 1H), 1.44 (s, 9H). GC-MS m/z 199 (M+). [a]D20=+96.9° (c 1.0, CHCl3) [literature (Aube, J.; Wolfe, M. S.; Yantiss, R. K.; Cook, S. M.; Takusagawa, F. Synthetic Communications 1992, 22, 3003-3012) [a]D25=+125° (c 0.2, CHCl3)]. is added the temperature below −68° C After the addition to warm slowly to room temperature overnight The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) the reaction is concentrated in vacuo to remove THF The mixture is extracted with EtOAc (3×150 mL) The combined organic portions are dried over sodium sulfate filtered concentrated to give 12.41 g of crude product as a yellow oil The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes)

反应条件: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of oxalyl chloride (6.47 mL, 74.5 mmol) in THF (166 mL) is cooled to −72° C. under nitrogen and treated dropwise with DMSO (10.59 mL, 149.1 mmol). The mixture is stirred for 5 min, whereupon tert-butyl (1S,2S)-2-hydroxycyclopentylcarbamate (10.0 g, 49.7 mmol) is added. Stirring is continued at −75° C. for 45 min. Triethylamine (37.4 mL, 268.3 mmol) is added slowly keeping the temperature below −68° C. After the addition is complete the reaction is allowed to warm slowly to room temperature overnight. The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) completed earlier. Water (100 mL) is added and the reaction is concentrated in vacuo to remove THF. The mixture is extracted with EtOAc (3×150 mL). The combined organic portions are dried over sodium sulfate, filtered, and concentrated to give 12.41 g of crude product as a yellow oil. The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes) to give the title compound (9.17 g, 93%). 1H-NMR (400 MHz, CDCl3) δ 5.04-5.02 (m, 1H), 3.98-3.96 (m, 1H), 2.65-2.63 (m, 1H), 2.44-2.39 (m, 1H), 2.21-2.11 (m, 1H), 2.04 (s, 1H), 1.89-1.85 (m, 1H), 1.66-1.59 (m, 1H), 1.44 (s, 9H). GC-MS m/z 199 (M+). [a]D20=+96.9° (c 1.0, CHCl3) [literature (Aube, J.; Wolfe, M. S.; Yantiss, R. K.; Cook, S. M.; Takusagawa, F. Synthetic Communications 1992, 22, 3003-3012) [a]D25=+125° (c 0.2, CHCl3)]. is added the temperature below −68° C After the addition to warm slowly to room temperature overnight The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) the reaction is concentrated in vacuo to remove THF The mixture is extracted with EtOAc (3×150 mL) The combined organic portions are dried over sodium sulfate filtered concentrated to give 12.41 g of crude product as a yellow oil The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl N-[(1S,2S)-2-trimethylsilyloxycyclopentyl]carbamate (15.5 g, 56.7 mmol) and tetrabutylammonium fluoride (85.0 mL, 85.0 mmol) in THF (113 mL) are stirred at room temperature for 1 h. Water (50 mL) is added and the mixture is concentrated in vacuo to remove the THF. The resulting mixture is extracted with EtOAc (3×75 mL). The combined organic portions are washed with brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated to give 14.7 g of crude product as a yellow oil. The material is purified on silica gel (330 g) using 25% EtOAc/hexanes to give the title compound as a white solid (10.25 g, 90%). LC-ES/MS m/z 224 (M+Na). the mixture is concentrated in vacuo to remove the THF The resulting mixture is extracted with EtOAc (3×75 mL) The combined organic portions are washed with brine (2×30 mL) dried over sodium sulfate filtered concentrated to give 14.7 g of crude product as a yellow oil The material is purified on silica gel (330 g)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl N-[(1S,2S)-2-trimethylsilyloxycyclopentyl]carbamate (15.5 g, 56.7 mmol) and tetrabutylammonium fluoride (85.0 mL, 85.0 mmol) in THF (113 mL) are stirred at room temperature for 1 h. Water (50 mL) is added and the mixture is concentrated in vacuo to remove the THF. The resulting mixture is extracted with EtOAc (3×75 mL). The combined organic portions are washed with brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated to give 14.7 g of crude product as a yellow oil. The material is purified on silica gel (330 g) using 25% EtOAc/hexanes to give the title compound as a white solid (10.25 g, 90%). LC-ES/MS m/z 224 (M+Na). the mixture is concentrated in vacuo to remove the THF The resulting mixture is extracted with EtOAc (3×75 mL) The combined organic portions are washed with brine (2×30 mL) dried over sodium sulfate filtered concentrated to give 14.7 g of crude product as a yellow oil The material is purified on silica gel (330 g)

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1S,2S)-trans-N-boc-2-aminocyclopentanol was dissolved in 50 ml THF and cooled to 10° C. To the reaction mixture were added 32.2 ml LiHMDS 1M in THF. After 1 hour 2.72 ml 2,4-difluoronitrobenzol were added and the mixture was stirred at rt overnight. Then the mixture was poured in water and extracted with ethylacetate. The organic layer was washed with water, dried and concentrated in vacuo. extracted with ethylacetate The organic layer was washed with water dried concentrated in vacuo

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1S,2S)-trans-N-boc-2-aminocyclopentanol was dissolved in 50 ml THF and cooled to 10° C. To the reaction mixture were added 32.2 ml LiHMDS 1M in THF. After 1 hour 2.72 ml 2,4-difluoronitrobenzol were added and the mixture was stirred at rt overnight. Then the mixture was poured in water and extracted with ethylacetate. The organic layer was washed with water, dried and concentrated in vacuo. extracted with ethylacetate The organic layer was washed with water dried concentrated in vacuo

反应条件: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of oxalyl chloride (6.47 mL, 74.5 mmol) in THF (166 mL) is cooled to −72° C. under nitrogen and treated dropwise with DMSO (10.59 mL, 149.1 mmol). The mixture is stirred for 5 min, whereupon tert-butyl (1S,2S)-2-hydroxycyclopentylcarbamate (10.0 g, 49.7 mmol) is added. Stirring is continued at −75° C. for 45 min. Triethylamine (37.4 mL, 268.3 mmol) is added slowly keeping the temperature below −68° C. After the addition is complete the reaction is allowed to warm slowly to room temperature overnight. The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) completed earlier. Water (100 mL) is added and the reaction is concentrated in vacuo to remove THF. The mixture is extracted with EtOAc (3×150 mL). The combined organic portions are dried over sodium sulfate, filtered, and concentrated to give 12.41 g of crude product as a yellow oil. The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes) to give the title compound (9.17 g, 93%). 1H-NMR (400 MHz, CDCl3) δ 5.04-5.02 (m, 1H), 3.98-3.96 (m, 1H), 2.65-2.63 (m, 1H), 2.44-2.39 (m, 1H), 2.21-2.11 (m, 1H), 2.04 (s, 1H), 1.89-1.85 (m, 1H), 1.66-1.59 (m, 1H), 1.44 (s, 9H). GC-MS m/z 199 (M+). [a]D20=+96.9° (c 1.0, CHCl3) [literature (Aube, J.; Wolfe, M. S.; Yantiss, R. K.; Cook, S. M.; Takusagawa, F. Synthetic Communications 1992, 22, 3003-3012) [a]D25=+125° (c 0.2, CHCl3)]. is added the temperature below −68° C After the addition to warm slowly to room temperature overnight The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) the reaction is concentrated in vacuo to remove THF The mixture is extracted with EtOAc (3×150 mL) The combined organic portions are dried over sodium sulfate filtered concentrated to give 12.41 g of crude product as a yellow oil The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl N-[(1S,2S)-2-trimethylsilyloxycyclopentyl]carbamate (15.5 g, 56.7 mmol) and tetrabutylammonium fluoride (85.0 mL, 85.0 mmol) in THF (113 mL) are stirred at room temperature for 1 h. Water (50 mL) is added and the mixture is concentrated in vacuo to remove the THF. The resulting mixture is extracted with EtOAc (3×75 mL). The combined organic portions are washed with brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated to give 14.7 g of crude product as a yellow oil. The material is purified on silica gel (330 g) using 25% EtOAc/hexanes to give the title compound as a white solid (10.25 g, 90%). LC-ES/MS m/z 224 (M+Na). the mixture is concentrated in vacuo to remove the THF The resulting mixture is extracted with EtOAc (3×75 mL) The combined organic portions are washed with brine (2×30 mL) dried over sodium sulfate filtered concentrated to give 14.7 g of crude product as a yellow oil The material is purified on silica gel (330 g)

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1S,2S)-trans-N-boc-2-aminocyclopentanol was dissolved in 50 ml THF and cooled to 10° C. To the reaction mixture were added 32.2 ml LiHMDS 1M in THF. After 1 hour 2.72 ml 2,4-difluoronitrobenzol were added and the mixture was stirred at rt overnight. Then the mixture was poured in water and extracted with ethylacetate. The organic layer was washed with water, dried and concentrated in vacuo. extracted with ethylacetate The organic layer was washed with water dried concentrated in vacuo

反应条件: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of oxalyl chloride (6.47 mL, 74.5 mmol) in THF (166 mL) is cooled to −72° C. under nitrogen and treated dropwise with DMSO (10.59 mL, 149.1 mmol). The mixture is stirred for 5 min, whereupon tert-butyl (1S,2S)-2-hydroxycyclopentylcarbamate (10.0 g, 49.7 mmol) is added. Stirring is continued at −75° C. for 45 min. Triethylamine (37.4 mL, 268.3 mmol) is added slowly keeping the temperature below −68° C. After the addition is complete the reaction is allowed to warm slowly to room temperature overnight. The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) completed earlier. Water (100 mL) is added and the reaction is concentrated in vacuo to remove THF. The mixture is extracted with EtOAc (3×150 mL). The combined organic portions are dried over sodium sulfate, filtered, and concentrated to give 12.41 g of crude product as a yellow oil. The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes) to give the title compound (9.17 g, 93%). 1H-NMR (400 MHz, CDCl3) δ 5.04-5.02 (m, 1H), 3.98-3.96 (m, 1H), 2.65-2.63 (m, 1H), 2.44-2.39 (m, 1H), 2.21-2.11 (m, 1H), 2.04 (s, 1H), 1.89-1.85 (m, 1H), 1.66-1.59 (m, 1H), 1.44 (s, 9H). GC-MS m/z 199 (M+). [a]D20=+96.9° (c 1.0, CHCl3) [literature (Aube, J.; Wolfe, M. S.; Yantiss, R. K.; Cook, S. M.; Takusagawa, F. Synthetic Communications 1992, 22, 3003-3012) [a]D25=+125° (c 0.2, CHCl3)]. is added the temperature below −68° C After the addition to warm slowly to room temperature overnight The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) the reaction is concentrated in vacuo to remove THF The mixture is extracted with EtOAc (3×150 mL) The combined organic portions are dried over sodium sulfate filtered concentrated to give 12.41 g of crude product as a yellow oil The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl N-[(1S,2S)-2-trimethylsilyloxycyclopentyl]carbamate (15.5 g, 56.7 mmol) and tetrabutylammonium fluoride (85.0 mL, 85.0 mmol) in THF (113 mL) are stirred at room temperature for 1 h. Water (50 mL) is added and the mixture is concentrated in vacuo to remove the THF. The resulting mixture is extracted with EtOAc (3×75 mL). The combined organic portions are washed with brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated to give 14.7 g of crude product as a yellow oil. The material is purified on silica gel (330 g) using 25% EtOAc/hexanes to give the title compound as a white solid (10.25 g, 90%). LC-ES/MS m/z 224 (M+Na). the mixture is concentrated in vacuo to remove the THF The resulting mixture is extracted with EtOAc (3×75 mL) The combined organic portions are washed with brine (2×30 mL) dried over sodium sulfate filtered concentrated to give 14.7 g of crude product as a yellow oil The material is purified on silica gel (330 g)