(S)-2-氨基-2-苯基乙酸甲酯

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

实验步骤: Using the general procedure for synthesizing naphthyl (aminoacid ester) phosphorochloridates, the HCl salt of (S)-methyl 2-amino-2-phenylacetate (2 g), naphthalen-1-yl phosphorodichloridate (2.59 g), TEA (2.76 mL) and DCM (60 mL) were combined to give (2S)-methyl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)-2-phenylacetate as a pale yellow thick oil. The crude compound was taken forward without further purification. for synthesizing naphthyl (aminoacid ester) phosphorochloridates

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

实验步骤: To a solution of 3-N,N-bis(4-methoxybenzyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine-3,6-diamine (0.1 g, 0.16 mmol) in anhydrous 1,4-dioxane (3 mL) was added CDI (0.13 g, 0.79 mmol) followed by the addition of imidazole (0.05 g, 0.78 mmol) and the contents were stirred at ambient temperature. After 16 h, DIPEA (0.12 mL, 0.64 mmol) and (S)-methyl-2-amino-2-phenylacetate (0.064 g, 0.32 mmol) were added and stirred. After 2 h, the reaction mixture was quenched with H2O and the organic contents were extracted with EtOAc (2×20 mL), dried over anhydrous Na2SO4 and concentrated. The residue thus obtained was purified by preparative HPLC to afford the title compound MS ES calc'd. for C51H46N6O5 [M+H]+ 823. Found 823. stirred After 2 h the reaction mixture was quenched with H2O the organic contents were extracted with EtOAc (2×20 mL) dried over anhydrous Na2SO4 concentrated The residue thus obtained was purified by preparative HPLC

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (S)-methyl 2-amino-2-phenylacetate (1.0 g, 6.06 mmol) in anhydrous MeOH (20 mL) was added 4-methoxy benzaldehyde (0.82 g, 6.06 mmol) and few drops of HOAc. After 30 min, the reaction mixture was cooled to 0° C., NaBH4 (0.69 g, 12.12 mmol) was added and the contents were stirred at ambient temperature. After 2 h, the reaction was quenched with ice cold H2O (10 mL), MeOH was removed under reduced pressure and the organic contents were extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (1×20 mL), dried over Na2SO4, concentrated and the residue thus obtained was taken directly for step 2. MS ES+APCI calc'd. for C17H19NO3 [M+H]+ 286. Found 286. After 2 h the reaction was quenched with ice cold H2O (10 mL), MeOH was removed under reduced pressure the organic contents were extracted with EtOAc (3×25 mL) The combined organic extracts were washed with brine (1×20 mL) dried over Na2SO4 concentrated the residue thus obtained

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (S)-methyl 2-amino-2-phenylacetate (1.0 g, 6.06 mmol) in anhydrous MeOH (20 mL) was added 4-methoxy benzaldehyde (0.82 g, 6.06 mmol) and few drops of HOAc. After 30 min, the reaction mixture was cooled to 0° C., NaBH4 (0.69 g, 12.12 mmol) was added and the contents were stirred at ambient temperature. After 2 h, the reaction was quenched with ice cold H2O (10 mL), MeOH was removed under reduced pressure and the organic contents were extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (1×20 mL), dried over Na2SO4, concentrated and (S)-methyl 2-((4-methoxybenzyl)amino)-2-phenylacetate thus obtained was taken directly for step 2. MS: [M+H]+ m/z 286. After 2 h the reaction was quenched with ice cold H2O (10 mL), MeOH was removed under reduced pressure the organic contents were extracted with EtOAc (3×25 mL) The combined organic extracts were washed with brine (1×20 mL) dried over Na2SO4 concentrated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (S)-methyl 2-amino-2-phenylacetate (1.0 g, 6.06 mmol) in anhydrous MeOH (20 mL) was added 4-methoxy benzaldehyde (0.82 g, 6.06 mmol) and few drops of HOAc. After 30 min, the reaction mixture was cooled to 0° C., NaBH4 (0.69 g, 12.12 mmol) was added and the contents were stirred at ambient temperature. After 2 h, the reaction was quenched with ice cold H2O (10 mL), MeOH was removed under reduced pressure and the organic contents were extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (1×20 mL), dried over Na2SO4, concentrated and (S)-methyl 2-((4-methoxybenzyl)amino)-2-phenylacetate thus obtained was taken directly for step 2. MS: [M+H]+ m/z 286. After 2 h the reaction was quenched with ice cold H2O (10 mL), MeOH was removed under reduced pressure the organic contents were extracted with EtOAc (3×25 mL) The combined organic extracts were washed with brine (1×20 mL) dried over Na2SO4 concentrated

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A catalytic amount of concentrated sulfuric acid (0.1 mL) was added to a 50 mL round bottom flask containing a solution of (S)-2-amino-2-phenylacetic acid (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (1.0 g, 6.6 mmol) in MeOH (10 mL). The resulting mixture was heated at 65° C. for 6 hours. The solvent was removed under reduced pressure, and the mixture was quenched with aqueous NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated to afford (S)-methyl 2-amino-2-phenylacetate (0.8 g, 74.0%) as a white solid. 1H NMR (300 MHz, CDCl3) δ: 7.37-7.32 (m, 5H), 4.62 (s, 1H), 3.70 (s, 3H). The solvent was removed under reduced pressure the mixture was quenched with aqueous NaHCO3 extracted with EtOAc The organic layer was dried over Na2SO4 filtered concentrated

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

实验步骤: (S)-(+)-2-Phenylglycine methyl ester (commercially available from Sigma-Aldrich, Milwaukee, Wis., 433 g, 2.146 mol) was added to a solution of 4-hydroxycyclohexanone (245 g, 2.146 mol) in DCE (8.5 L). Sodium triacetoxyborohydride was added (910 g, 4.292 mol), and the mixture was stirred at room temperature under nitrogen for 23 hours. Water (3 L) was added to quench the reaction, and the organic layer was separated. The aqueous phase was extracted with DCM (4 L×2) and the organic layers were combined, dried, filtered and concentrated. The residue was purified by column chromatography (gradient elution with 100% DCM to DCM/MeOH=25:1) to afford (S)-methyl 2-((4-hydroxycyclohexyl)amino)-2-phenylacetate (197 g, 35%) (mixture of cis and trans). m/z (ESI) 264 (M+H)+. to quench the reaction the organic layer was separated The aqueous phase was extracted with DCM (4 L×2) dried filtered concentrated The residue was purified by column chromatography (gradient elution with 100% DCM to DCM/MeOH=25:1)

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

实验步骤: (S)-(+)-2-Phenylglycine methyl ester (commercially available from Sigma-Aldrich, Milwaukee, Wis., 433 g, 2.146 mol) was added to a solution of 4-hydroxycyclohexanone (245 g, 2.146 mol) in DCE (8.5 L). Sodium triacetoxyborohydride was added (910 g, 4.292 mol), and the mixture was stirred at room temperature under nitrogen for 23 hours. Water (3 L) was added to quench the reaction, and the organic layer was separated. The aqueous phase was extracted with DCM (4 L×2) and the organic layers were combined, dried, filtered and concentrated. The residue was purified by column chromatography (gradient elution with 100% DCM to DCM/MeOH=25:1) to afford (S)-methyl 2-((4-hydroxycyclohexyl)amino)-2-phenylacetate (197 g, 35%) (mixture of cis and trans). m/z (ESI) 264 (M+H)+. to quench the reaction the organic layer was separated The aqueous phase was extracted with DCM (4 L×2) dried filtered concentrated The residue was purified by column chromatography (gradient elution with 100% DCM to DCM/MeOH=25:1)

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

实验步骤: Using the general procedure for synthesizing naphthyl (aminoacid ester) phosphorochloridates, the HCl salt of (S)-methyl 2-amino-2-phenylacetate (2 g), naphthalen-1-yl phosphorodichloridate (2.59 g), TEA (2.76 mL) and DCM (60 mL) were combined to give (2S)-methyl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)-2-phenylacetate as a pale yellow thick oil. The crude compound was taken forward without further purification. for synthesizing naphthyl (aminoacid ester) phosphorochloridates

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

实验步骤: In analogy to Example 2, but using only one mole equivalent of triethylamine, 4.45 g (27 mmol) of D/L-phenylglycine methyl ester were reacted with 3.51 g (22 mmol) of 2-chloro-3-nitropyridine. Working up and column chromatography (n-heptane/acetone/methyl t-butyl ether=5:1:1) resulted in 3.27 g (42%) of N-(3-nitro-2-pyridyl)-(D/L)-phenylglycine methyl ester of melting point 70° C.

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

实验步骤: In analogy to Example 2, but using only one mole equivalent of triethylamine, 4.45 g (27 mmol) of D/L-phenylglycine methyl ester were reacted with 3.51 g (22 mmol) of 2-chloro-3-nitropyridine. Working up and column chromatography (n-heptane/acetone/methyl t-butyl ether=5:1:1) resulted in 3.27 g (42%) of N-(3-nitro-2-pyridyl)-(D/L)-phenylglycine methyl ester of melting point 70° C.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-methyl 2-amino-2-phenylacetate (5 g, 24.8 mmol, 1 equiv) was dissolved in a mixture of 48% hydrogen bromide (13 ml, 198 mmol, 8 equiv) and water (19 ml). An aqueous solution of sodium nitrite (5.48 g, 79.36 mmol, 3.2 equiv) was added slowly and the mixture stirred at 0° C. for 1.5 h. The reaction was degassed in vacuo and extracted with ether. The organic layer was further washed with water and brine, dried over MgSO4, and concentrated in vacuo. The resulting residue was purified using the Biotage flash chromatography system (SNAP 100 g cartridge, Rf=0.5, gradient—1%-10% ethyl acetate in hexanes) to afford the (R)-methyl 2-bromo-2-phenylacetate as a light yellow oil (2.3 g, 40% yield); 1H NMR (400 MHz, DMSO-d6): δ 3.72 (s, 3H); 5.95 (s, 1H); 7.36-7.42 (m, 3H); 7.54 (d, 2H, J=1.6 Hz); 7.56 (d, 1H, J=2 Hz); MS for C9H9BrO2 m/z 229.98 (M+H)+. The reaction was degassed in vacuo extracted with ether The organic layer was further washed with water and brine dried over MgSO4 concentrated in vacuo The resulting residue was purified