反应详情

In a 250-mL round-bottomed flask, a solution of (R)-1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1.51 g, 4.57 mmol, ASW Medchem, New Brunswick, N.J.), 3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (0.684 g, 4.57 mmol, Advanced Chemblocks, Burlingame, Calif.), and Hünig's base (1.76 mL, 10.06 mmol) in 15 mL of DMF was stirred at 0° C. To this mixture was added HATU (1.912 g, 5.03 mmol, Oakwood Products, West Columbia, S.C.). The reaction was stirred for 3 h at room temperature. The mixture was then diluted with EtOAc (25 mL) and water (25 mL). The organic solution was then extracted with water (2×25 mL) and brine (25 mL). The organic layer was dried over MgSO4, filtered, and concentrated. The crude material was purified via column chromatography (about 40 g silica gel, 5% to 80% of EtOAc in hexanes) to give (R)-di-tert-butyl 2-((1R,5S)-3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)piperazine-1,4-dicarboxylate (1.78 g) as a colorless oil.

1. extractionThe organic solution was then extracted with water (2×25 mL) and brine (25 mL)
2. dry with materialThe organic layer was dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe crude material was purified via column chromatography (about 40 g silica gel, 5% to 80% of EtOAc in hexanes)