反应详情

Diisopropylethylamine (14 mL, 80.6 mmol) was added to a cooled (˜0° C.) solution of 2,6-dichloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid (Example 29; 7.44 g, 21.9 mmol), 3-[[(1,1-dimethylethoxy)carbonyl]amino]-L-alanine, methyl ester, hydrochloride (6.15 g, 24.1 mmol), HOBT (3.12 g, 22.8 mmol), and HBTU (8.64 g, 22.8 mmol) in N,N-dimethylformamide (200 mL). The mixture was stirred at room temperature for 16 h. The solvent was evaporated and ethyl acetate (200 mL) was added. The solution was washed with 1 M HCl (100 mL) and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate, and brine (200 mL each), dried (MgSO4), filtered, evaporated, and chromatographed (70% ethyl acetate/hexanes) to give N-[2,6-dichloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[[(1,1-dimethylethoxy)carbonyl]amino]-L-alanine, methyl ester (8.64 g, 73%) as a white foam.

1. customThe solvent was evaporated
2. additionethyl acetate (200 mL) was added
3. washThe solution was washed with 1 M HCl (100 mL)
4. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
5. washThe combined organic layers were washed with saturated aqueous sodium hydrogen carbonate, and brine (200 mL each)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customevaporated
9. customchromatographed (70% ethyl acetate/hexanes)