3,4-Difluorobenzaldehyde → HCID 24753616, compound

HRID 420810Notes

Reaction equation

HRID 420810 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[C:10]([C:18](=[O:20])[CH3:19])=[C:9]1[CH:21]([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][C:32]=1[F:33])[CH:28]=O>CCO.[OH-].[Na+]>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[C:10]([C:18](=[O:20])/[CH:19]=[CH:28]/[C:27]2[CH:30]=[CH:31][C:32]([F:33])=[C:25]([F:24])[CH:26]=2)=[C:9]1[CH:21]([CH3:23])[CH3:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 5880883,4-Difluorobenzaldehyde2×HCID 24753518HCID 24753518, compound2×

Product 1

HCID 24753616HCID 24753616, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
60 °C

Procedure

General Procedure G. To a solution of 1-(1-benzyl-5-hydroxy-2-isopropyl-1H-indol-3-yl)ethanone (Compound 29, 64 mg, 0.21 mmol) in EtOH (3 ml) and NaOH (4 M, 0.53 ml) at room temperature was added 3,4-difluorobenzaldehyde (46 μl, 0.42 mmol). The reaction was stirred for 16 h, heated to 60° C. for 4 h, and more 3,4-difluorobenzaldehyde (180 μl, 1.68 mmol) was added, stirred at room temperature for 24 h. The reaction was quenched by 1 M HCl (5 ml), and stirred at room temperature for 4 h, and the product was extracted with EtOAc. The layers were separated and the organic layer was washed with brine, and dried over Na2SO4, and concentrated under vacuum. The residue was purified by flash chromatography on silica gel eluting with 0-30% EtOAc-hexanes followed by PTLC (30% EtOAc-hexanes) to yield (E)-1-(1-benzyl-5-hydroxy-2-isopropyl-1H-indol-3-yl)-3-(3,4-difluorophenyl)prop-2-en-1-one (Compound 30) as a yellow solid.

Workup

  1. stirringstirred at room temperature for 24 h
  2. customThe reaction was quenched by 1 M HCl (5 ml)
  3. stirringstirred at room temperature for 4 h
  4. extractionthe product was extracted with EtOAc
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by flash chromatography on silica gel eluting with 0-30% EtOAc-hexanes

Sources & evidence

ORD record
ord-c4fadc232b1543f780dee9324a34e6b2
Source dataset
uspto-grants-2012_01
Patent number
US08097644B2

Reaction notes

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