tert-butyl N-[(1R)-2-amino-1-phenylethyl]carbamate

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

実験手順: Using a similar hydrogenolysis procedure to that described as Deprotection Method A, (R)-2-(Boc-amino)-2-phenylethylazide (32.5 g, 124 mmol) in methanol (200 mL) and THF (300 mL) afforded, after chromatography (SiO2, 10:5:1 CH2Cl2, EtOAc, triethylamine), 24.0 g (82%) of the title compound afforded

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

実験手順: Using a similar hydrogenolysis procedure to that described as Deprotection Method A, (R)-2-(Boc-amino)-2-phenylethylazide (32.5 g, 124 mmol) in methanol (200 mL) and THF (300 mL) afforded, after chromatography (SiO2, 10:5:1 CH2Cl2, EtOAc, triethylamine), 24.0 g (82%) of the title compound. afforded

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

実験手順: A solution of the crude phthalimide and hydrazine hydrate (10.0 ml, 177 mmol) in EtOH (200 ml) was stirred at reflux for 1 hour. Once cooled, the mixture was concentrated under reduced pressure. The residue was suspended in 1.5M HCl (200 ml) and washed with CH2Cl2 (50 ml×3). The organic solution was extracted with 4M HCl (50 ml×2). The combined aqueous extracts were made basic with 10M NaOH (100 ml) and extracted with CH2Cl2 (50 ml×4). This organic solution was dried (Na2SO4), filtered and concentrated under reduced pressure. Purification gave ((R)-2-amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester as an off-white solid (2.41 g, 51% over 2 steps). at reflux for 1 hour Once cooled the mixture was concentrated under reduced pressure washed with CH2Cl2 (50 ml×3) The organic solution was extracted with 4M HCl (50 ml×2) extracted with CH2Cl2 (50 ml×4) This organic solution was dried (Na2SO4) filtered concentrated under reduced pressure Purification

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a degassed solution of ((R)-2-amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester (400 mg, 1.69 mmol) in toluene (10 ml), was added 2-nitroiodobenzene (423 mg, 1.69 mmol), Pd2 (dba)3 (31 mg, 0.34 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyxanthene (39 mg, 0.68 mmol) and Cs2CO3 (551 mg, 1.69 mmol). The mixture was heated at 110° C. for 24 h. It was then concentrated and the residue was purified using column chromatography (4:1, Hexanes/EtOAc) to give [(R)-2-(2-nitro-phenylamino)-1-phenyl-ethyl]-carbamic acid tert-butyl ester (390 mg, 64%). It was then concentrated the residue was purified

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

実験手順: Following general procedure A: ((R)-2-amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester (269 mg, 1.14 mmol), tetrahydro-4H-pyran-4-one (0.12 ml, 1.3 mmol) and NaBH(OAc)3 (340 mg, 1.60 mmol) in CH2Cl2 (8.0 ml) was stirred at room temperature for 18 hours. Standard work-up and purification by flash column chromatography on silica (CH2Cl2/MeOH, 19:1) gave [(R)-1-phenyl-2-(tetrahydro-pyran-4-ylamino)-ethyl]-carbamic acid tert-butyl ester as a colorless oil (333 mg, 91%). 1H NMR (CDCl3) δ 0.80-1.36 (m, 3H), 1.41 (s, 9H), 1.68-1.82 (m, 2H), 2.61 (tt, 1H, J=10.3, 4.1 Hz), 2.93 (d, 2H, J=5.1 Hz), 3.35 (tdd, 2H, J=11.6, 5.6, 2.2 Hz), 3.88-3.96 (m, 2H), 4.74 (br s, 1H), 5.45 (br d, 1H, J=5.7 Hz), 7.22-7.35 (m, 5H). Standard work-up and purification by flash column chromatography on silica (CH2Cl2/MeOH, 19:1)

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

実験手順: Using general procedure E, ((R)-2-amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester (616 mg, 2.61 mmol) and tetrahydro-pyran-4-carboxylic acid (339 mg, 2.61 mmol) afforded ((R)-1-phenyl-2-[(tetrahydro-pyran-4-carbonyl)-amino]ethyl)-carbamic acid tert-butyl ester (908 mg, 99%).

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

実験手順: Using general procedure A, ((R)-2-amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester (472 mg, 2.00 mmol) and 2-methylpropionaldehyde (181 μL, 2.00 mmol) afforded ((R)-2-(2-methylpropyl)amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester (533 mg, 91%).