methyl (2R)-piperidine-2-carboxylate;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of (S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoic acid (2.26 g, 6.68 mmol) in DCM (50 mL) was added (R)-methyl piperidine-2-carboxylate HCl salt (1.00 g, 5.57 mmol), followed by EDC (1.60 g, 8.35 mmol), HOBT (1.71 g, 11.1 mmol), and TEA (2.33 mL, 16.7 mmol). The reaction mixture was stirred at rt for 6 hr. The reaction mixture was diluted with water and extracted with EtOAc (2×30 mL). The combined EtOAc layers were washed with water and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 30-70% EtOAc/Hex to give (R)-methyl 1-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoyl)piperidine-2-carboxylate (1.80 g, 3.88 mmol, 69.8% yield) as a white foam. Anal. Calcd. for C23H33N3O7 m/z 463.5. found: 464.3 (M+H)+. extracted with EtOAc (2×30 mL) The combined EtOAc layers were washed with water and saturated aqueous NaCl dried over Na2SO4 filtered concentrated The crude product was purified eluting with a gradient of 30-70% EtOAc/Hex

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl (2R)-2-piperidinecarboxylate hydrochloride (1.0 g, 5.56 mmol) and HOBt (0.90 g, 6.67 mmol) in CH2Cl2 (20 mL) was added 4-methylmorpholine (2.44 mL, 22.24 mmol), N-{[(phenylmethyl)oxy]carbonyl}glycine (1.16 g, 5.56 mmol), and EDCI (1.28 g, 6.67 mmol). After stirring overnight, the solution was washed 6 N aq. HCl (100 mL) and water (100 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), and then dried over anhydrous MgSO4 and concentrated in vacuo to provide methyl (2R)-1-(N-{[(phenylmethyl)oxy]carbonyl}glycyl)-2-piperidinecarboxylate (2.029 g, 99%). LCMS: (M+H)+: 335.1. the solution was washed 6 N aq. HCl (100 mL) and water (100 mL) The aqueous layer was extracted with CH2Cl2 (3×50 mL) The combined organic layers were washed with water (50 mL) and brine (50 mL) dried over anhydrous MgSO4 concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of (S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoic acid (2.26 g, 6.68 mmol) in DCM (50 mL) was added (R)-methyl piperidine-2-carboxylate HCl salt (1.00 g, 5.57 mmol), followed by EDC (1.60 g, 8.35 mmol), HOBT (1.71 g, 11.1 mmol), and TEA (2.33 mL, 16.7 mmol). The reaction mixture was stirred at rt for 6 hr. The reaction mixture was diluted with water and extracted with EtOAc (2×30 mL). The combined EtOAc layers were washed with water and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 30-70% EtOAc/Hex to give (R)-methyl 1-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoyl)piperidine-2-carboxylate (1.80 g, 3.88 mmol, 69.8% yield) as a white foam. Anal. Calcd. for C23H33N3O7 m/z 463.5. found: 464.3 (M+H)+. extracted with EtOAc (2×30 mL) The combined EtOAc layers were washed with water and saturated aqueous NaCl dried over Na2SO4 filtered concentrated The crude product was purified eluting with a gradient of 30-70% EtOAc/Hex