4-bromo-1H-indole-2-carboxylic acid → tert-butyl 4-bromo-1H-indole-2-carboxylate

HRID 460005Notes

Reaction equation

HRID 460005 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([OH:13])=[O:12])[NH:6]2>C1(C)C=CC=CC=1.C(OC(N(C)C)OC(C)(C)C)(C)(C)C>[C:3]([O:12][C:11]([C:5]1[NH:6][C:7]2[C:3]([CH:4]=1)=[C:2]([Br:1])[CH:10]=[CH:9][CH:8]=2)=[O:13])([CH3:7])([CH3:4])[CH3:2]

Participants

4

Reactant 1

HCID 40426044-bromo-1H-indole-2-carboxylic acid

Product 1

HCID 68857000tert-butyl 4-bromo-1H-indole-2-carboxylate

Reagents, catalysts & solvents 2

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

Procedure

To 7 g 4-Bromo-1H-indole-2-carboxylic acid in 150 ml toluene, 28 ml Di-tert-butoxymethyl-dimethyl-amine were added dropwise at 80° C. The reaction mixture was heated under reflux for additional 12 h. After removal of the solvents under reduced pressure the residue was dissolved in 200 ml DCM and washed with sat. aqueous NaHCO3 solution (2×50 ml). The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with n-heptane/ethyl acetate 9:1. The fractions containing the product were collected and concentrated under reduced pressure. Yield: 6.5 g . MS (ESI+): m/e=297.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for additional 12 h
  3. customAfter removal of the solvents under reduced pressure the residue
  4. dissolutionwas dissolved in 200 ml DCM
  5. washwashed with sat. aqueous NaHCO3 solution (2×50 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 n-heptane/ethyl acetate 9:1
  9. additionThe fractions containing the product
  10. customwere collected
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fb5e8b52e8cb4f6d9c8776744cf2ac13
Source dataset
uspto-grants-2007_03
Patent number
US07196103B2

Reaction notes

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