Methanol → 1H-Indole-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester

HRID 1071690Notes

Reaction equation

HRID 1071690 reaction equation
[C:1]([O:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[C:14](Br)[CH:13]=[CH:12][CH:11]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][OH:19].CN([CH:23]=[O:24])C>CCN(CC)CC.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:18][O:19][C:23]([C:14]1[C:15]2[CH:16]=[C:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[NH:9][C:10]=2[CH:11]=[CH:12][CH:13]=1)=[O:24]

Participants

7

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 68857000tert-butyl 4-bromo-1H-indole-2-carboxylate

Product 1

HCID 688587391H-Indole-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 7.3 g 4-Bromo-1H-indole-2-carboxylic acid tert-butyl ester in 100 ml DMF, 6.8 ml NEt3, 276 mg Pd(OAc)2, 128 mg 1,1′-Bis(diphenylphosphino)ferrocene, 12 ml MeOH were added and purged with argon for 15 min. This solution was then purged with carbon monoxide and heated to 70° C. for 4 h. The reaction mixture was concentrated under reduced pressure, the residue dissolved in 200 ml DCM and washed with 100 ml water. The organic layer was dried over MgSO4 and, after removal of the solvent 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.

Workup

  1. custompurged with argon for 15 min
  2. customThis solution was then purged with carbon monoxide
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in 200 ml DCM
  5. washwashed with 100 ml water
  6. dry with materialThe organic layer was dried over MgSO4
  7. customafter removal of the solvent 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-443db0542ad04468b56af5d85d449233
Source dataset
uspto-grants-2005_06
Patent number
US06906084B2

Reaction notes

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