反应详情

(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoic acid (1.2 equiv), HATU (1.4 equiv) and 2,6-lutidine (2.0 equiv) were combined in DMF (0.2 M vs aniline). tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate (1.0 equiv) was dissolved in DMF (0.11 M) and was added to the reaction mixture. The reaction was stirred at room temperature for 18 h and ethyl acetate and saturated sodium bicarbonate were added. Aqueous layer was extracted twice with ethyl acetate and combined organic layers were washed with brine, 10% aqueous lithium chloride, 1N HCl, brine, dried (Na2SO4), filtered and concentrated. The crude product was purified using automated silica-gel flash chromatography using a solvent gradient of 5% to 60% of ethyl acetate and hexanes.

1. additionwas added to the reaction mixture
2. extractionAqueous layer was extracted twice with ethyl acetate
3. washwere washed with brine, 10% aqueous lithium chloride, 1N HCl, brine
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product was purified