5-(methoxycarbonyl)-1H-indole-2-carboxylic acid → 2-(tert-Butyl)5-methyl1H-indole-2,5-dicarboxylate

HRID 459999Notes

Reaction equation

HRID 459999 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([OH:16])=[O:15])=[CH:8]2)=[O:4]>C1(C)C=CC=CC=1.C(OC(N(C)C)OC(C)(C)C)(C)(C)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([O:16][C:5]([CH3:6])([CH3:13])[CH3:3])=[O:15])=[CH:8]2)=[O:4]

Participants

4

Reactant 1

HCID 529879165-(methoxycarbonyl)-1H-indole-2-carboxylic acid

Product 1

HCID 685647962-(tert-Butyl)5-methyl1H-indole-2,5-dicarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 5477121,1-bis(1,1-dimethylethoxy)-N,N,N-trimethylamineSolvent

Procedure

To 13 g 1H-Indole-2,5-dicarboxylic acid 5-methyl ester in 300 ml toluene, 59 ml Di-tert-butoxymethyl-dimethyl-amine were added dropwise at 80° C. Then, the reaction mixture was heated under reflux for additional 6 h. After removal of the solvents under reduced pressure the residue was dissolved in 300 ml DCM and washed with sat. aqueous NaHCO3 solution (2×100 ml). The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with a n-heptane/ethyl acetate gradient. The fractions containing the product were collected and concentrated under reduced pressure. Yield: 8.3 g. MS (ES+): m/e=276.

Workup

  1. temperatureThen, the reaction mixture was heated
  2. temperatureunder reflux for additional 6 h
  3. customAfter removal of the solvents under reduced pressure the residue
  4. dissolutionwas dissolved in 300 ml DCM
  5. washwashed with sat. aqueous NaHCO3 solution (2×100 ml)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel eluting with a n-heptane/ethyl acetate gradient
  9. additionThe fractions containing the product
  10. customwere collected
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bb10148e3fda410994757dc044c9b9a2
Source dataset
uspto-grants-2007_03
Patent number
US07196103B2

Reaction notes

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