Methyl vinyl ketone → 4-(5-Fluoro-1h-indol-3-yl)butan-2-one

HRID 2382040Notes

Reaction equation

HRID 2382040 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH:11]([C:13]([CH3:15])=[O:14])=[CH2:12]>CC#N.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Sc+3]>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:12][CH2:11][C:13](=[O:14])[CH3:15]

Participants

5

Reactant 2

HCID 6570Methyl vinyl ketoneHCID 678615-Fluoroindole

Product 1

HCID 226629314-(5-Fluoro-1h-indol-3-yl)butan-2-oneYield 70%

Reagents, catalysts & solvents 2

HCID 2734571Scandium(III) triflateCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of 5-fluoroindole (10.5 g, 78 mmol) in MeCN (150 mL) at 0° C. is treated with methyl vinyl ketone (9.5 mL, 117 mmol) and Sc(OTf)3 (383 mg, 0.78 mmol) and stirred for 1 h. The mixture is then stirred an additional 6 h at rt. The mixture is concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-50% EtOAc in heptane to afford 4-(5-fluoro-1H-indol-3-yl)-butan-2-one (11.1 g, 70%).

Workup

  1. stirringThe mixture is then stirred an additional 6 h at rt
  2. concentrationThe mixture is concentrated in vacuo
  3. customThe residue is purified by silica gel chromatography
  4. washeluting with 10%-50% EtOAc in heptane

Sources & evidence

ORD record
ord-6406398197634da6bf760234a20e04a3
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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