反应详情

温度

-20 °C

To a solution of (1R,2R)-2-{[3-{[[((3R,4S)-1-(tert-butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)-amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropanecarboxylic acid (1 eq.) from Example 4/Step 1 in DCM (0.1 M) at −20° C. was added N-methylmorpholine (1.3 eq.) and isobutylchloroformate (1.3 eq.). The reaction was stirred at −20° C. for 45 min. Meanwhile, a solution of indan-5-ol (2 eq) in THF (0.2) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 1 eq.), stirred for 30 min at rt, and added to the reaction at −15° C. The reaction was stirred at rt for 18 h and then quenched with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex) to afford the title compound as an oil.

1. customat −20° C.
2. stirringstirred for 30 min at rt
3. additionadded to the reaction at −15° C
4. stirringThe reaction was stirred at rt for 18 h
5. customquenched with saturated aqueous NaHCO3 solution
6. extractionThe aqueous layer was extracted with EtOAc
7. washThe combined organic extracts were washed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex)