1-Propanol → propyl 3-[3-(2-oxo-2-propoxyethyl)-1H-indol-2-yl]propanoate

HRID 476223Notes

Reaction equation

HRID 476223 reaction equation
CS(O)(=O)=O.O=[C:7]1[N:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)N=[C:10](CCC(OCC)=O)[CH2:9][CH2:8]1.[OH-:26].[Na+].[CH2:28]([OH:31])[CH2:29][CH3:30]>>[O:31]=[C:28]([O:31][CH2:28][CH2:29][CH3:30])[CH2:29][C:30]1[C:14]2[C:13](=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH:12][C:7]=1[CH2:8][CH2:9][C:10]([O:31][CH2:28][CH2:29][CH3:30])=[O:26]

Participants

5

Reactant 4

HCID 10311-PropanolHCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 21630617Ethyl 3-(6-oxo-1-phenyl-1,4,5,6-tetrahydropyridazin-3-yl)propanoate

Product 1

HCID 59487250propyl 3-[3-(2-oxo-2-propoxyethyl)-1H-indol-2-yl]propanoateYield 79%

Conditions

Temperature
80 °C

Procedure

Methanesulfonic acid (1.15 equiv.) was added to a stirred solution of ethyl 3-(6-oxo-1-phenyl-1,4,5,6-tetrahydropyridazin-3-yl)propanoate from Step 1 in n-propanol (1.1 M). The mixture was stirred overnight at 80° C. The mixture was cooled to room temperature and neutralized with aqueous 1N NaOH (1 equiv.). Final mixture was concentrated under vacuum, diluted with toluene and concentrated again. The residue was purified by column chromatography on silica gel using automatized gradiant pump system CombiFlashRF (Teledyne ISCO) eluting with ethyl acetate/hexane (0:100 to 60:40) to give the title compound (79%) as a brown oil.

Workup

  1. concentrationFinal mixture was concentrated under vacuum
  2. additiondiluted with toluene
  3. concentrationconcentrated again
  4. customThe residue was purified by column chromatography on silica gel using automatized gradiant pump system CombiFlashRF (Teledyne ISCO)
  5. washeluting with ethyl acetate/hexane (0:100 to 60:40)

Sources & evidence

ORD record
ord-0b4718e0eecc4e0bb88ad95c30455e85
Source dataset
uspto-grants-2014_01
Patent number
US08637671B2

Reaction notes

Loading…