反应详情

Bis(trifluoroacetoxy)iodobenzene (44.4 g, 103.2 mmol) was added to a solution of N-[(1,1-dimethylethoxy)carbonyl]-L-asparagine (Boc-Asn; 20.00 g, 86.1 mmol) in N,N-dimethylformamide/water (2:1; 300 mL). The solution was stirred at room temperature for 30 min and then pyridine (10 mL, 123.6 mmol) was added. The solution was stirred at room temperature for 4.5 h and then the solvent was evaporated (45° C., ˜0.5 mm Hg). The residue was dissolved in acetone/water (1:1; 400 mL) and sodium hydrogen carbonate (31.8 g, 378.5 mmol) and 1-[[(9H-fluoren-9-ylmethoxy)carbonyl]oxy]-2,5-pyrrolidinedione (Fmoc-OSu; 34.74 g, 103.0 mmol) were added. The mixture was stirred at room temperature overnight, then the acetone was evaporated and the mixture was acidified to pH 1 with 1 M HCl and extracted with ethyl acetate (200 mL, then 100 mL). The combined organic layers were washed with brine (3×50 mL), dried (Na2SO4), filtered, evaporated (45° C., ˜0.5 mm Hg), and chromatographed (50-60% ethyl acetate/hexanes) to give N-[(1,1-dimethylethoxy)carbonyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine (32.33 g, 88%) as a white solid.

1. stirringThe solution was stirred at room temperature for 4.5 h
2. customthe solvent was evaporated (45° C., ˜0.5 mm Hg)
3. dissolutionThe residue was dissolved in acetone/water (1:1; 400 mL)
4. stirringThe mixture was stirred at room temperature overnight
5. customthe acetone was evaporated
6. extractionextracted with ethyl acetate (200 mL
7. washThe combined organic layers were washed with brine (3×50 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated (45° C., ˜0.5 mm Hg)
11. customchromatographed (50-60% ethyl acetate/hexanes)