反应详情

A solution of ester 388D (482 mg, 0.866 mmol) in TFA/CH2Cl2/H2O (5 ml, 48/48/4) was stirred for 1 h at rt, concentrated, the resulting residue was rotavaped with chloroform twice and CH2Cl2 once to give acid intermediate as a yellow solid. The solid was dissolved in 1,2-dichloroethane (5 ml), glycine t-butyl ester hydrochloride (203 mg, 1.21 mmol), DMAP (52.9 mg, 0.433 mmol) and DIEA (528 μl, 3.03 mmol) were added. The mixture was stirred 3 min until homogeneous, then EDC.HCl (249 mg, 1.30 mmol) was added. The reaction mixture was stirred for 2 h, concentrated, partitioned between EtOAc (50 ml) and 1N HCl (50 ml). The organic layer were washed with 1N HCl (30 ml), the combined aqueous wash layer was extracted with EtOAc (3×50 ml), the combined organic layer was washed with brine (100 ml), dried with Na2SO4 and concentrated. The residue was purified by silica gel flash column chromatography to afford a yellow crystalline solid 388 (372 mg, 70%)(10%-25% EtOAc—CH2Cl2). LCMS Found: (M+H)+=613.6; (M−tBu+2H)+=558.2

1. concentrationconcentrated
2. customCH2Cl2 once to give acid intermediate as a yellow solid
3. additionwas added
4. concentrationconcentrated
5. custompartitioned between EtOAc (50 ml) and 1N HCl (50 ml)
6. washThe organic layer were washed with 1N HCl (30 ml)
7. extractionthe combined aqueous wash layer was extracted with EtOAc (3×50 ml)
8. washthe combined organic layer was washed with brine (100 ml)
9. dry with materialdried with Na2SO4
10. concentrationconcentrated
11. customThe residue was purified by silica gel flash column chromatography