3-氧代吗啉-4-羧酸叔丁酯

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Tert-butyl 3-oxomorpholine-4-carboxylate (5.2 g, 25.8 mmol) was dissolved in dry THF (52 ml). The mixture was cooled to −30° C. and (bis(trimethylsilyl)amino) lithium (1M THF solution, 28.4 ml, 28.4 mmol) was added dropwise. The resulting mixture was stirred for 1 hr, then diphenyl phosphorochloridate (7.3 g, 27.1 mmol) was added dropwise. The resulting mixture was allowed to warm slowly to ambient temperature over 6 hrs, after which time no starting material was present by HPLC. The reaction mixture was poured into saturated ammonium chloride solution (100 ml) and diluted with ethyl acetate (100 ml). The organic phase was separated and washed with sat NaHCO3 (50 ml), then brine (50 ml), dried (MgSO4), filtered and concentrated. The residue was purified on silica gel, eluting with 25-30% ethyl acetate/petrol. This gave the title compound as an oil which solidified on standing (7.59 g, 68%); 1H-NMR (CDCl3) 1.35 (9H, s), 3.54 (2H, dt), 3.87 (2H, m), 6.26 (1H, s), 7.11-7.17 (6H, m), 7.24-7.28 (4H, m); 31P-NMR (CDCl3)-16.07; 13C-NMR (CDCl3) 28.1, 42.0, 65.8, 120.0, 120.03, 120.09, 120.13, 125.19, 125.61, 125.62, 129.6, 129.86, 129.9; MS ES(+) 378.0 (M+-tBu). to warm slowly to ambient temperature over 6 hrs The organic phase was separated washed with sat NaHCO3 (50 ml) brine (50 ml), dried (MgSO4) filtered concentrated The residue was purified on silica gel eluting with 25-30% ethyl acetate/petrol

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

实验步骤: Morpholin-3-one (35 g, 346.2 mmol) was slurried in dry THF (350 ml). Tert-butoxycarbonyl tert-butyl carbonate (105.8 g, 111.4 mmol) was added, followed by DMAP (4.2 g, 34.6 mmol). The mixture began to degass rapidly over 30 minutes. The resulting orange solution was stirred at ambient temperature for 24 hrs. The mixture was then cooled in an ice bath and imidazole (23.57 g, 346.2 mmol) was added. After stirring for 30 minutes ethyl acetate (500 ml) was added. The organic phase was separated and washed with 1% (v/v) HCl (500 ml), then sat NaHCO3 (500 ml), then brine (200 ml), dried (MgSO4), filtered and concentrated. The crude was purified through a plug of silica gel, eluting with ethyl acetate. The filtrate was evaporated to give an oil. 40/60 pet ether (200 ml) was added slowly with stirring to generate a white solid. The mixture was aged for 30 minutes, cooled briefly in an ice bath and filtered, washing with 40/60 pet ether. Tert-butyl 3-oxomorpholine-4-carboxylate was obtained as a white solid which was dried under vacuum (52.7 g, 76%); 1H-NMR (CDCl3) 1.47 (9H, s), 3.68 (2H, m), 3.82 (2H, m), 4.15 (2H, s); MS ES(+) 145.8 (M+-tBu). to degass rapidly over 30 minutes The mixture was then cooled in an ice bath was added The organic phase was separated washed with 1% (v/v) HCl (500 ml) brine (200 ml), dried (MgSO4) filtered concentrated The crude was purified through a plug of silica gel eluting with ethyl acetate The filtrate was evaporated to give an oil with stirring The mixture was aged for 30 minutes cooled briefly in an ice bath filtered washing with 40/60 pet ether