HCID 58172045, compound → HCID 58172101, compound

HRID 560177Notes

Reaction equation

HRID 560177 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1[CH2:15][CH2:16][CH2:17][NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:12][C:11]([O:26]CC1C=CC=CC=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2].[H][H]>CN(C=O)C.CCO.[OH-].[OH-].[Pd+2]>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1[CH2:15][CH2:16][CH2:17][NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:12][C:11]([OH:26])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

6

Reactant 2

HCID 58172045HCID 58172045, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 58172101HCID 58172101, compoundYield 41.8%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

5-Benzyloxy-3-[3-(t-butoxycarbonylamino)-propyl]-1H-indole-2-carboxylic acid ethyl ester (170 mg, 0.37 mmol, 1.0 equiv) was dissolved in the mixture of DMF (3 mL) and EtOH (18 mL) and 30 mg of 20% Pd(OH)2 on carbon was added. The reaction was subjected to 40 psi of hydrogen gas in Parr apparatus for 10 h. The catalyst was filtered off over diatomaceous earth and the ethanol was removed on the rotovap. The residue was taken up in EtOAc and washed 3×20 ml, of brine. The organic layer was dried (Na2SO4), filtered, and evaporated. The crude product is a mixture of starting material and product. The crude residue was purified by flash chromatography on silica using 0% EtOAc in hexanes graded to 30% EtOAc in hexanes as the mobile phase to yield 5-hydroxy-3-[3-(t-butoxycarbonylamino)-propyl]-1H-indole-2-carboxylic acid ethyl ester (56 mg, 41%). This material was used without further manipulation.

Workup

  1. additionwas added
  2. filtrationThe catalyst was filtered off over diatomaceous earth
  3. customthe ethanol was removed on the rotovap
  4. washwashed 3×20 ml
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. additiona mixture of starting material and product
  9. customThe crude residue was purified by flash chromatography on silica using 0% EtOAc in hexanes

Sources & evidence

ORD record
ord-371275fad29041eea264f87790dfe85a
Source dataset
uspto-grants-2011_11
Patent number
US08063094B2

Reaction notes

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