反应详情

温度

0 °C

N-methylmorpholine (1.1 equiv.) was added dropwise over 1 h to a stirred, mixture of 3-[3-(2-oxo-2-propoxyethyl)-1H-indol-2-yl]propanoic acid from Step 3 and ethyl chloroformate (1.11 equiv.) in THF (0.4 M) cooled to 0° C. The reaction temperature was closely monitored during the addition and was not allowed to go over +2° C. The mixture was stirred at 0° C. an additional 30 min. A white precipitate formed rapidly. Diazomethane (0.3 M in Et2O, 1.8 equiv.) was added and the final mixture was stirred for 2 h at 0° C. The mixture was filtered and the supernatant was concentrated under vacuum (with AcOH put in the vacuum trap to quench excess diazomethane). The residue was purified by column chromatography on silica gel using a CombiFlashRF (Teledyne ISCO) eluting with EtOAc/Hex (10:90 to 60:40) to give the title compound (63%) as a yellow solid.

1. additionThe reaction temperature was closely monitored during the addition
2. customto go over +2° C
3. customA white precipitate formed rapidly
4. filtrationThe mixture was filtered
5. concentrationthe supernatant was concentrated under vacuum (with AcOH
6. customto quench excess diazomethane)
7. customThe residue was purified by column chromatography on silica gel using a CombiFlashRF (Teledyne ISCO)
8. washeluting with EtOAc/Hex (10:90 to 60:40)