Sodium Carbonate → methyl 3-(1-methylethyl)-7-nitro-1H-indole-5-carboxylate

HRID 852610

Reaction equation

HRID 852610 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([N+:25]([O-:27])=[O:26])[C:12]=1[N:13]([CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])C(=O)C(F)(F)F)[C:5]([O:7][CH2:8]C)=[O:6].C(O[Na])=O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:24][CH:22]([C:21]1[C:2]2[C:12](=[C:11]([N+:25]([O-:27])=[O:26])[CH:10]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=2)[NH:13][CH:20]=1)[CH3:23]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 86602879Ethyl 3-bromo-4-[(3-methyl-2-buten-1-yl)(trifluoroacetyl)amino]-5-nitrobenzoateHCID 178526064HCID 178526064, compound

Product 1

HCID 69358662methyl 3-(1-methylethyl)-7-nitro-1H-indole-5-carboxylateYield 135.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-bromo-4-[(3-methyl-2-buten-1-yl)(trifluoroacetyl)amino]-5-nitrobenzoate (D215) (12.9 g, 28.5 mmol, 1 equiv) in DMF (130 ml) were added HCOONa (1.94 g, 28.5 mmol, 1 equiv), Na2CO3 (7.54 g, 71.2 mmol, 2.5 equiv), Bu4NCI (8.7 g, 31.3 mmol, 1.1 equiv) and palladium (II) acetate (320 mg, 1.42 mmol, 0.05 equiv) and the resulting mixture was stirred under nitrogen for 1 h then cooled to room temperature and concentrated in vacuo. The residue was partitioned between AcOEt and H2O and the two layers were separated. The insoluble material in the aqueous phase was filtered off through a pad of celite and the aqueous layer extracted twice with AcOEt. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo to give methyl 3-(1-methylethyl)-7-nitro-1H-indole-5-carboxylate (D218) (10.1 g, 128%) as a black solid which was used in the next step without further purification.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between AcOEt and H2O
  3. customthe two layers were separated
  4. filtrationThe insoluble material in the aqueous phase was filtered off through a pad of celite
  5. extractionthe aqueous layer extracted twice with AcOEt
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1296be22aad6463db62bdfedbffd8138
Source dataset
uspto-grants-2007_08
Patent number
US07253198B2

Linked notes

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