tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of methyltriphenylphosphonium bromide (5.3 g, 14.8 mmol) in THF (50 mL) was cooled to 0° C. under nitrogen. Potassium hexamethyl disilazide (27.7 mL, 0.5M toluene solution, 13.9 mmol) was added and the mixture was stirred for 30 min. A solution of (1-t-butoxycarbonylpiperidin-4-yl)acetaldehyde from Step A (2.25 g, 9.9 mmol) in THF (10 mL) was added and the mixture was warmed to rt. After 30 min, the reaction was complete by tlc analysis. The mixture was diluted with ethyl acetate (200 mL) and washed with water and brine (100 mL each). The organic phase was dried over sodium sulfate and concentrated to give an oil which was purified by FC (75 g silica, 10/1 hexane/ethyl acetate) to afford the title compound (1.61 g). After 30 min washed with water and brine (100 mL each) The organic phase was dried over sodium sulfate concentrated to give an oil which was purified by FC (75 g silica, 10/1 hexane/ethyl acetate)

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

実験手順: A solution of methyltriphenylphosphonium bromide (5.3 g, 14.8 mmol) in THF (50 mL) was cooled to 0° C. under nitrogen. Potassium hexamethyl disilazide (27.7 mL, 0.5M toluene solution, 13.9 mmol) was added and the mixture was stirred for 30 min. A solution of (1-t-butoxycarbonylpiperidin-4-yl)acetaldehyde from Step A (2.25 g, 9.9 mmol) in THF (10 mL) was added and the mixture was warmed to rt. After 30 min, the reaction was complete by tlc analysis. The mixture was diluted with ethyl acetate (200 mL) and washed with water and brine (100 mL each). The organic phase was dried over sodium sulfate and concentrated to give an oil which was purified by FC (75 g silica, 10/1 hexane/ethyl acetate) to afford the title compound (1.61 g). After 30 min washed with water and brine (100 mL each) The organic phase was dried over sodium sulfate concentrated to give an oil which was purified by FC (75 g silica, 10/1 hexane/ethyl acetate)

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

実験手順: A solution of oxalyl chloride (1.23 mL, 14.1 mmol) in methylene chloride (50 mL) was cooled to −78° C. DMSO (2.0 mL, 28.3 mmol), was added slowly via syringe. After 10 min, 4-(2-hydroxyeth-1-yl)-1-t-butoxycarbonylpiperidine (2.7 g, 11.8 mmol) in methylene chloride (15 mL) was added. The cold mixture was stirred for an additional 20 min then TEA (8.2 mL, 59 mmol) was added. The mixture was warmed to rt and stirred for 1.5 h, then diluted with methylene chloride (300 mL). The organic phase was washed with 1M sodium hydroxide, dried over sodium sulfate and concentrated. FC (125 g silica, 2.5/1 hexanes/ethyl acetate) afforded the title compound (2.25 g). stirred for 1.5 h The organic phase was washed with 1M sodium hydroxide dried over sodium sulfate concentrated

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

実験手順: A solution of oxalyl chloride (1.23 mL, 14.1 mmol) in methylene chloride (50 mL) was cooled to −78° C. DMSO (2.0 mL, 28.3 mmol), was added slowly via syringe. After 10 min, 4-(2-hydroxyeth-1-yl)-1-t-butoxycarbonylpiperidine (2.7 g, 11.8 mmol) in methylene chloride (15 mL) was added. The cold mixture was stirred for an additional 20 min then TEA (8.2 mL, 59 mmol) was added. The mixture was warmed to rt and stirred for 1.5 h, then diluted with methylene chloride (300 mL). The organic phase was washed with 1M sodium hydroxide, dried over sodium sulfate and concentrated. FC (125 g silica, 2.5/1 hexanes/ethyl acetate) afforded the title compound (2.25 g). stirred for 1.5 h The organic phase was washed with 1M sodium hydroxide dried over sodium sulfate concentrated

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

実験手順: A solution of CH2Cl2 (200 mL) was treated with pyridiniumchlorochromate (PCC) (6.7 g, 0.031 mol) for five minutes. Solid NaOAc (2.55 g, 0.031 mol) and 4Å molecular sieves were added, followed by a solution of 4-1 (4.75 g, 0.02 mol) in CH2Cl2 (50 mL). The reaction was stirred for 3 h, diluted with 400 mL of Et2O, and filtered through a pad of silica gel. The silica gel was washed with 1 L of Et2O and 0.5 L of 1:1 Et2O/CHCl3. The organic solutions were combined, concentrated to give a greenish oil which was filtered through another pad of silica gel, eluting with 1.2 L of Et2O. The filtrate was concentrated to give 4-2 as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 9.77 (s, 1H), 4.08 (bd, 2H), 2.7 (bt, 2H), 2.37 (dd, 2H), 2.03 (m, 1H), 1.7 (bd, 2H), 1.42 (s, 9H), 1.2 (m, 2H). ##STR32## Methyl 2-(S)-benzyloxycarbonylamino-3-aminopropionate hydrochloride (5-2) filtered through a pad of silica gel The silica gel was washed with 1 L of Et2O and 0.5 L of 1:1 Et2O/CHCl3 concentrated to give a greenish oil which was filtered through another pad of silica gel eluting with 1.2 L of Et2O The filtrate was concentrated

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

実験手順: A solution of CH2Cl2 (200 mL) was treated with pyridiniumchlorochromate (PCC) (6.7 g, 0.031 mol) for five minutes. Solid NaOAc (2.55 g, 0.031 mol) and 4Å molecular sieves were added, followed by a solution of 4-1 (4.75 g, 0.02 mol) in CH2Cl2 (50 mL). The reaction was stirred for 3 h, diluted with 400 mL of Et2O, and filtered through a pad of silica gel. The silica gel was washed with 1 L of Et2O and 0.5 L of 1:1 Et2O/CHCl3. The organic solutions were combined, concentrated to give a greenish oil which was filtered through another pad of silica gel, eluting with 1.2 L of Et2O. The filtrate was concentrated to give 4-2 as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 9.77 (s, 1H), 4.08 (bd, 2H), 2.7 (bt, 2H), 2.37 (dd, 2H), 2.03 (m, 1H), 1.7 (bd, 2H), 1.42 (s, 9H), 1.2 (m, 2H). ##STR32## Methyl 2-(S)-benzyloxycarbonylamino-3-aminopropionate hydrochloride (5-2) filtered through a pad of silica gel The silica gel was washed with 1 L of Et2O and 0.5 L of 1:1 Et2O/CHCl3 concentrated to give a greenish oil which was filtered through another pad of silica gel eluting with 1.2 L of Et2O The filtrate was concentrated