N-(叔丁氧基羰基)-N-环己基甘氨酸

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

实验步骤: A solution of N-(t-butyloxycarbonyl)cyclohexylglycine (2.0 g, 7.77 mmol) in anhydrous THF (10 mL) was cooled to 0° C. Borane solution (1 M in THF, 15.5 mL, 15.5 mmol) was added slowly and the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with MeOH (5 mL), volatiles were evaporated and the residue was partitioned between water and EtOAc. The organic layer was washed with saturated NaHCO3/water, brine, dried (sodium sulfate), and evaporated to give tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 4a (1.26 g, 66.7% ), MS (CI) m/z 144.2 (MH+-Boc). The reaction was quenched with MeOH (5 mL), volatiles were evaporated the residue was partitioned between water and EtOAc The organic layer was washed with saturated NaHCO3/water, brine dried (sodium sulfate) evaporated

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

实验步骤: A solution of 40 g (0.119 mole) of BOC-CYCLOHEXYLGLYCINE, O,N-DIMETHYLHYDROXAMIDE in 550 ml Et2O was cooled in ice and 148 ml (0.148 mole) of a 1M solution of LiAlH4 in Et2O added over 0.5 hour. After an additional 15 minutes, the mixture was treated cautiously with 28 g of KHSO4 in 100 ml H2O. The mixture was filtered through Celite and washed with 10% citric acid and saturated NaHCO3. After drying the solvent was removed under reduced pressure to give the crude BOC-CYCLOHEXYLGLYCINAL. The material was used immediately in the following reaction. ##STR175## The mixture was filtered through Celite washed with 10% citric acid and saturated NaHCO3 After drying the solvent was removed under reduced pressure

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

实验步骤: A solution of 40 g (0.119 mole) of BOC-CYCLOHEXYLGLYCINE, O,N-DIMETHYLHYDROXAMIDE in 550 ml Et2O was cooled in ice and 148 ml (0.148 mole) of a 1M solution of LiAlH4 in Et2O added over 0.5 hour. After an additional 15 minutes, the mixture was treated cautiously with 28 g of KHSO4 in 100 ml H2O. The mixture was filtered through Celite and washed with 10% citric acid and saturated NaHCO3. After drying the solvent was removed under reduced pressure to give the crude BOC-CYCLOHEXYLGLYCINAL. The material was used immediately in the following reaction. ##STR207## The mixture was filtered through Celite washed with 10% citric acid and saturated NaHCO3 After drying the solvent was removed under reduced pressure

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

实验步骤: Under a nitrogen atmosphere, 5% rhodium/alumina (3.00 g) is added to a solution of DL-N-tert-butoxycarbonylphenylglycine in ethanol (80 ml). The atmosphere is replaced with pressurized hydrogen (4.0 kgf/cm2) and stirred for ten days. The 5% rhodium/alumina is filtered out. The filtrate is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to give the titled reference compound (25.0 g). The 5% rhodium/alumina is filtered out The filtrate is concentrated under reduced pressure the residue is purified by silica gel column chromatography

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

实验步骤: Under a nitrogen atmosphere, 5% rhodium/alumina (3.00 g) is added to a solution of DL-N-tert-butoxycarbonylphenylglycine in ethanol (80 ml). The atmosphere is replaced with pressurized hydrogen (4.0 kgf/cm2) and stirred for ten days. The 5% rhodium/alumina is filtered out. The filtrate is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to give the titled reference compound (25.0 g). The 5% rhodium/alumina is filtered out The filtrate is concentrated under reduced pressure the residue is purified by silica gel column chromatography

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

实验步骤: A solution of N-(t-butyloxycarbonyl)cyclohexylglycine (2.0 g, 7.77 mmol) in anhydrous THF (10 mL) was cooled to 0° C. Borane solution (1 M in THF, 15.5 mL, 15.5 mmol) was added slowly and the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with MeOH (5 mL), volatiles were evaporated and the residue was partitioned between water and EtOAc. The organic layer was washed with saturated NaHCO3/water, brine, dried (sodium sulfate), and evaporated to give tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 4a (1.26 g, 66.7% ), MS (CI) m/z 144.2 (MH+-Boc). The reaction was quenched with MeOH (5 mL), volatiles were evaporated the residue was partitioned between water and EtOAc The organic layer was washed with saturated NaHCO3/water, brine dried (sodium sulfate) evaporated

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

实验步骤: A solution of N-(t-butyloxycarbonyl)cyclohexylglycine (2.0 g, 7.77 mmol) in anhydrous THF (10 mL) was cooled to 0° C. Borane solution (1 M in THF, 15.5 mL, 15.5 mmol) was added slowly and the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with MeOH (5 mL), volatiles were evaporated and the residue was partitioned between water and EtOAc. The organic layer was washed with saturated NaHCO3/water, brine, dried (sodium sulfate), and evaporated to give tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 4a (1.26 g, 66.7% ), MS (CI) m/z 144.2 (MH+-Boc). The reaction was quenched with MeOH (5 mL), volatiles were evaporated the residue was partitioned between water and EtOAc The organic layer was washed with saturated NaHCO3/water, brine dried (sodium sulfate) evaporated

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

实验步骤: A solution of 40 g (0.119 mole) of BOC-CYCLOHEXYLGLYCINE, O,N-DIMETHYLHYDROXAMIDE in 550 ml Et2O was cooled in ice and 148 ml (0.148 mole) of a 1M solution of LiAlH4 in Et2O added over 0.5 hour. After an additional 15 minutes, the mixture was treated cautiously with 28 g of KHSO4 in 100 ml H2O. The mixture was filtered through Celite and washed with 10% citric acid and saturated NaHCO3. After drying the solvent was removed under reduced pressure to give the crude BOC-CYCLOHEXYLGLYCINAL. The material was used immediately in the following reaction. ##STR175## The mixture was filtered through Celite washed with 10% citric acid and saturated NaHCO3 After drying the solvent was removed under reduced pressure

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

实验步骤: A solution of N-(t-butyloxycarbonyl)cyclohexylglycine (2.0 g, 7.77 mmol) in anhydrous THF (10 mL) was cooled to 0° C. Borane solution (1 M in THF, 15.5 mL, 15.5 mmol) was added slowly and the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with MeOH (5 mL), volatiles were evaporated and the residue was partitioned between water and EtOAc. The organic layer was washed with saturated NaHCO3/water, brine, dried (sodium sulfate), and evaporated to give tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 4a (1.26 g, 66.7%), MS (CI) m/z 144.2 (MH+-Boc). The reaction was quenched with MeOH (5 mL), volatiles were evaporated the residue was partitioned between water and EtOAc The organic layer was washed with saturated NaHCO3/water, brine dried (sodium sulfate) evaporated

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

实验步骤: A solution of N-(t-butyloxycarbonyl)cyclohexylglycine (2.0 g, 7.77 mmol) in anhydrous THF (10 mL) was cooled to 0° C. Borane solution (1 M in THF, 15.5 mL, 15.5 mmol) was added slowly and the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with MeOH (5 mL), volatiles were evaporated and the residue was partitioned between water and EtOAc. The organic layer was washed with saturated NaHCO3/water, brine, dried (sodium sulfate), and evaporated to give tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 4a (1.26 g, 66.7%), MS (CI) m/z 144.2 (MH+-Boc). The reaction was quenched with MeOH (5 mL), volatiles were evaporated the residue was partitioned between water and EtOAc The organic layer was washed with saturated NaHCO3/water, brine dried (sodium sulfate) evaporated

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

实验步骤: A solution of N-(t-butyloxycarbonyl)cyclohexylglycine (2.0 g, 7.77 mmol) in anhydrous THF (10 mL) was cooled to 0° C. Borane solution (1 M in THF, 15.5 mL, 15.5 mmol) was added slowly and the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with MeOH (5 mL), volatiles were evaporated and the residue was partitioned between water and EtOAc. The organic layer was washed with saturated NaHCO3/water, brine, dried (sodium sulfate), and evaporated to give tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 2a (1.26 g, 66.7%), MS (CI) m/z 144.20 (MH+-Boc). The reaction was quenched with MeOH (5 mL), volatiles were evaporated the residue was partitioned between water and EtOAc The organic layer was washed with saturated NaHCO3/water, brine dried (sodium sulfate) evaporated

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

实验步骤: Boc-N-(cyclohexyl)glycine benzyl ester (14.0 g, 40 mmol) was dissolved in 240 mL anhydrous ethanol, flushed with dry nitrogen and combined carefully under inert atmosphere with 1.5 g of 10% palladium on carbon. Using a Parr apparatus the nitrogen atmosphere was replaced with hydrogen (43 P.S.I.) and the mixture was shaken over 24 hours at room temperature. The mixture was purged with nitrogen and the catalyst and solids were removed by filtration through a pad of celite. The filtrate was concentrated by rotary evaporation and the residue was taken up in 300 mL of ethyl acetate. The ethyl acetate layer was extracted with 150 mL of 1N sodium hydroxide solution. The basic solution was acidified in an ice bath to pH 3 with 1N hydrochloric acid solution. The acid solution was extracted with ethyl acetate (3×100 mL). This solution was washed with saturated sodium chloride solution and concentrated in vacuo to a colorless oil which was further dried under high vacuum. The resulting glass/solid was triturated with hexane, which after filtration and drying provided the title compound (8.89 g) as a colorless powder. M.P. 103-104 C (uncorr.) Anal. (C13H23NO4) C, H, N; C: calcd., 60.68; found, 60.77 H; calcd., 9.01; found, 9.20. N: calcd., 5.44; found, 5.44. flushed with dry nitrogen The mixture was purged with nitrogen the catalyst and solids were removed by filtration through a pad of celite The filtrate was concentrated by rotary evaporation The ethyl acetate layer was extracted with 150 mL of 1N sodium hydroxide solution The basic solution was acidified in an ice bath to pH 3 with 1N hydrochloric acid solution The acid solution was extracted with ethyl acetate (3×100 mL) This solution was washed with saturated sodium chloride solution concentrated in vacuo to a colorless oil which was further dried under high vacuum The resulting glass/solid was triturated with hexane, which after filtration drying