反应详情

To a mixture of the glycine tert-butyl ester hydrogen chloride salt (70) (484 mg, 2.9 mmol) in dichloromethane (25 mL) was added Fmoc-Gly-OH (71) (0.861 mg, 2.99 mmol), DIPEA (756 mg, 4.35 mmol) and HATU (1.3 g, 3.5 mmol). The reaction mixture was stirred at an ambient temperature for 16 h and then poured into ethyl acetate and was washed with water (3×) and brine (1×). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified via radial chromatography on a 2 mm plate eluting with 5% methanol/dichloromethane. Product containing fractions were concentrated under reduced pressure and treated with 20% piperidine/dichloromethane (10 mL) for 1 h, before being concentrated under reduced pressure and then purified twice via radial chromatography on a 2 mm plate eluting with a gradient of 5 to 10% methanol/dichloromethane to provide (200 mg, 37%): 1H-NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 4.00 (s, 2H), 3.39 (s, 2H), 1.47 (s, 9H).

1. washwas washed with water (3×) and brine (1×)
2. dry with materialThe organic phase was dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified via radial chromatography on a 2 mm plate
6. washeluting with 5% methanol/dichloromethane
7. additionProduct containing fractions
8. concentrationwere concentrated under reduced pressure
9. additiontreated with 20% piperidine/dichloromethane (10 mL) for 1 h
10. concentrationbefore being concentrated under reduced pressure
11. custompurified twice via radial chromatography on a 2 mm plate
12. washeluting with a gradient of 5 to 10% methanol/dichloromethane
13. customto provide (200 mg, 37%)