Hydrochloric Acid → Methyl 8-bromo-6-fluoro-2,3-dihydro-1-oxo-1H-pyrrolo[1,2-a]indole-2-carboxylate

HRID 857335

Reaction equation

HRID 857335 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:12]([O:14]C)=O)[NH:6]2.CC(C)([O-])C.[K+].[C:22]([O:26][CH3:27])(=[O:25])[CH:23]=[CH2:24].Cl>C1COCC1.C1(C)C=CC=CC=1.C1COCC1>[Br:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:12](=[O:14])[CH:23]([C:22]([O:26][CH3:27])=[O:25])[CH2:24][N:6]3[C:7]=2[CH:8]=[C:9]([F:11])[CH:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 21867463Methyl 4-bromo-6-fluoro-1H-indole-2-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 58760711Methyl 8-bromo-6-fluoro-2,3-dihydro-1-oxo-1H-pyrrolo[1,2-a]indole-2-carboxylateYield 81.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

To a suspension of the indole of Step 4 (4 g, 15 mmol) in a mixture of 10:1 toluene/THF (100 mL) at r.t. was added potassium t-butoxide (15 mL of a 1M solution in THF). The reaction mixture was stirred for 2 minutes and methyl acrylate (2.5 g, 30 mmol) was added. The mixture was stirred at reflux for 5 hours and cooled to r.t. Then 1N HCl was added to acidify to pH 3 and the reaction mixture was extracted with EtOAc and the combined organic layers were concentrated. The residue was swished in EtOAc/Hexanes to give 4 g of the desired compound as a pale yellow solid.

Workup

  1. stirringThe mixture was stirred
  2. temperatureat reflux for 5 hours
  3. extractionthe reaction mixture was extracted with EtOAc
  4. concentrationthe combined organic layers were concentrated

Sources & evidence

ORD record
ord-c9e472e8bbb3439bab0a1350f149cf54
Source dataset
uspto-grants-2006_12
Patent number
US07144913B2

Linked notes

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