反应详情

To a 0° C. solution of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propanoate (4 g, 12.56 mmol) and cesium carbonate (4.50 g, 13.82 mmol) in DMF (40 mL) was added tert-butyl 2-bromoacetate (2.015 mL, 13.82 mmol) and was allowed to warm up to RT by removing from ice bath and stirred for 18 hrs. The reaction was poured into 1:1 ice water:1N HCl and extracted with EtOAc. The organic layer washed with brine, collected, dried over MgSO4, filtered and evaporated to give the crude product. The crude product was purified via silica gel chromatography (80 g column, 0-50% EtOAc:Hexanes over 20 CV) to get the product (S)-methyl 3-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-indol-3-yl)-2-((tert-butoxycarbonyl)amino)propanoate (4.69 g, 86% yield). 1H NMR (400 MHz, chloroform-d) d 7.56 (d, J=7.8 Hz, 1H), 7.26-7.18 (m, 2H), 7.17-7.12 (m, 1H), 6.92 (s, 1H), 5.09 (d, J=7.6 Hz, 1H), 4.71 (s, 2H), 3.73-3.59 (m, 3H), 3.30 (d, J=5.1 Hz, 2H), 1.45 (s, 18H). ESI-MS(+) m/z=433 (M+H).

1. customby removing from ice bath
2. additionThe reaction was poured into 1:1 ice water
3. extraction1N HCl and extracted with EtOAc
4. washThe organic layer washed with brine
5. customcollected
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customto give the crude product
10. customThe crude product was purified via silica gel chromatography (80 g column, 0-50% EtOAc:Hexanes over 20 CV)