Diethyl Malonate → (+/-)-Ethyl 8-bromo-1-(2-ethoxy-2-oxoethyl)-6-fluoro-3-oxo-2,3-dihydro-1h-pyrrolo[1,2-a]indole-2-carboxylate

HRID 857398Notes

Reaction equation

HRID 857398 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5]CC)=O.C[O-].[Na+].[CH2:15]([O:17][C:18](=[O:32])[CH:19]=[CH:20][C:21]1[NH:22][C:23]2[C:28]([CH:29]=1)=[C:27]([Br:30])[CH:26]=[C:25]([F:31])[CH:24]=2)[CH3:16].[NH4+].[Cl-]>CCO>[Br:30][C:27]1[C:28]2[CH:29]=[C:21]3[CH:20]([CH2:19][C:18]([O:17][CH2:15][CH3:16])=[O:32])[CH:2]([C:1]([O:9][CH2:10][CH3:11])=[O:8])[C:3](=[O:5])[N:22]3[C:23]=2[CH:24]=[C:25]([F:31])[CH:26]=1

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 69561024ethyl-3-(4-bromo-6-fluoro-1H-indol-2-yl)prop-2-enoate

Product 1

HCID 91021522(+/-)-Ethyl 8-bromo-1-(2-ethoxy-2-oxoethyl)-6-fluoro-3-oxo-2,3-dihydro-1h-pyrrolo[1,2-a]indole-2-carboxylateYield 89.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of diethyl malonate (1.67 g, 10.4 mmol) in EtOH (30 mL) at r.t. was added sodium methoxide (2.26 mL, 25% solution in MeOH). The mixture was stirred for 5 minutes and a solution of the compound of Step 3 (1.3 g, 4.2 mmol) in EtOH (10 mL) was added. The mixture was stirred at 75° C. for 12 hours, saturated aqueous NH4Cl was added and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 20% EtOAc to give 1.6 g of the title compound.

Workup

  1. stirringThe mixture was stirred at 75° C. for 12 hours
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluted with 20% EtOAc

Sources & evidence

ORD record
ord-788d03ed6a9f4e1f99f937b6413ae2fa
Source dataset
uspto-grants-2006_12
Patent number
US07144913B2

Reaction notes

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