反应详情

To a mixture of L-proline-tert-butyl ester hydrogen chloride salt 75 (0.5 g, 2.9 mmol) in dichloromethane (50 mL) was added 76 (0.98 g, 2.99 mmol), DIPEA (756 mg, 4.35 mmol) and HATU (1.3 g, 3.5 mmol). The reaction mixture was allowed to stir at an ambient temperature for 16 h. The mixture was poured into ethyl acetate (100 mL) and was washed with 0.2 N HCl (50 mL), water (50 mL), brine (50 mL) and dried over MgSO4. Chromatography was conducted on a 2 mm radial chromatotron plate eluting with 10% ethyl acetate in hexanes. Product-containing fractions were concentrated under reduced pressure, dissolved in dichloromethane (8 mL) and treated with piperidine (2 mL). The mixture was stirred for 1 h, concentrated under reduced pressure and purified on a 2 mm radial chromatotron plate eluting with 5% methanol/dichloromethane. This gave 200 mg (26%) of the dipeptide 74: 1H-NMR (400 MHz, CDCl3) δ 4.41 (m, 1H), 4.17 (m, 1H), 3.82 (m, 1H), 3.57 (m, 4H), 3.2 (m, 1H), 2.82 (m, 1H), 2.83-1.65 (m, 5H), 1.44 (m, 9H).

1. washwas washed with 0.2 N HCl (50 mL), water (50 mL), brine (50 mL)
2. dry with materialdried over MgSO4
3. washeluting with 10% ethyl acetate in hexanes
4. concentrationProduct-containing fractions were concentrated under reduced pressure
5. dissolutiondissolved in dichloromethane (8 mL)
6. additiontreated with piperidine (2 mL)
7. stirringThe mixture was stirred for 1 h
8. concentrationconcentrated under reduced pressure
9. custompurified on a 2 mm radial chromatotron plate
10. washeluting with 5% methanol/dichloromethane