反应详情

A flame dried flask was charged with Fmoc-D-Valine (200 mg, 0.59 mmol) and 5.9 mL anhydrous THF. N-hydroxysuccinimide (75 mg, 0.65 mmol) was added, followed by diisopropylcarbodiimide (0.1 mL, 0.65 mmol), and the reaction was stirred at an ambient temperature overnight, at which time LC-MS revealed conversion to product. The reaction mixture was diluted with CH2Cl2 and washed with water (50 mL), brine (50 mL), dried over sodium sulfate and concentrated to dryness. The material was carried forward without further purification. LC-MS: tR 13.89 min, m/z (ES+) found 437.0 (M+H)+. Crude Fmoc-D-Val-OSu (0.59 mmol) was dissolved in dimethoxyethane (1.5 mL) and THF (0.8 mL). D-alanine (73 mg, 0.89 mmol) was dissolved in 2.3 mL water and added to the reaction mixture, followed by sodium bicarbonate (99 mg, 1.2 mmol). The resulting slurry was stirred at room temperature overnight, at which time the reaction had clarified and LC-MS revealed completion. The reaction was poured into 50 mL CH2Cl2 and the organic layer was washed with 50 mL 0.1 M HCl and then brine, dried over sodium sulfate, and then concentrated to dryness. The crude product was purified by radial chromatography on a 1 mm chromatotron plate eluted with CH2Cl2 to provide 60 (128 mg, 54%). TLC: Rf=0.18, 10% MeOH in CH2Cl2. Analytical HPLC (0.1% formic acid): tR 9.47 min. LC-MS: tR 13.09 min, m/z (ES+) found 411.1 (M+H)+, m/z (ES−) found 409.2 (M−H)−.

1. customA flame dried flask
2. washwashed with water (50 mL), brine (50 mL)
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated to dryness
5. customThe material was carried forward without further purification
6. additionadded to the reaction mixture
7. stirringThe resulting slurry was stirred at room temperature overnight, at which time the reaction
8. washthe organic layer was washed with 50 mL 0.1 M HCl
9. dry with materialbrine, dried over sodium sulfate
10. concentrationconcentrated to dryness
11. customThe crude product was purified by radial chromatography on a 1 mm chromatotron plate
12. washeluted with CH2Cl2