反应详情

To a solution of (R)-2-(1-Benzyl-cyclopropylmethyl)-succinic acid 1-methyl ester (2.453 g, 8.88 mmol), di-isopropyl amine (1.1 eq, 9.76 mmol, 1.26 g) and morpholine (1.5 eq., 13.3 mmol, 1.16 g) in dry dichloromethane under N2 was added PyBOP (1.1 eq., 9.76 mmol, 5.08 g). The mixture was stirred at room temperature for 5 hr, and concentrated in vacuum. The residue was dissolved in ethyl acetate (150 mL) and washed with water (100 mL), NH4Cl (100 mL), NaHCO3 (2×100 mL), then water (100 mL). The organic layer was dried (MgSO4) and concentrated in vacuum. The residue was purified over 120 g silica gel, eluted with ethyl acetate:heptane (1:1.5, 1:1, to 2:1) to afford the desired compound contaminated with PyBOP residues. A solution of the mixture in ether containing ethyl acetate (250 mL total) was washed with dilute HCl (150 mL), water (150 mL) dilute NaOH (150 mL) then water (150 mL). The organic layer was dried (MgSO4) and concentrated in vacuum to afford (R)-2-(1-Benzyl-cyclopropylmethyl)-4-morpholin-4-yl-4-oxo-butyric acid methyl ester as a white solid (2.292 g, 74.7% yield).

1. concentrationconcentrated in vacuum
2. dissolutionThe residue was dissolved in ethyl acetate (150 mL)
3. washwashed with water (100 mL), NH4Cl (100 mL), NaHCO3 (2×100 mL)
4. dry with materialThe organic layer was dried (MgSO4)
5. concentrationconcentrated in vacuum
6. customThe residue was purified over 120 g silica gel
7. washeluted with ethyl acetate:heptane (1:1.5, 1:1, to 2:1)