Trifluoroacetic acid → 4-Fluoro-2-methyl-1h-indole

HRID 2278519Notes

Reaction equation

HRID 2278519 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[C:10]([CH2:23][C:24](=O)[CH3:25])=[C:11]([NH:15]C(=O)OC(C)(C)C)[CH:12]=[CH:13][CH:14]=1.C(=O)([O-])O.[Na+]>ClCCl>[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:10]=1[CH:23]=[C:24]([CH3:25])[NH:15]2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86699261Tert-butyl [3-fluoro-2-(2-oxopropyl)phenyl]carbamate

Product 1

HCID 224900334-Fluoro-2-methyl-1h-indoleYield 97.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1.43 ml of trifluoroacetic acid are added to a solution of 0.35 g of tert-butyl [3-fluoro-2-(2-oxopropyl)phenyl]carbamate in 13 ml of anhydrous dichloromethane at ambient temperature. The reaction mixture is then stirred at ambient temperature for 24 h, and is then diluted with 27 ml of dichloromethane and treated with 25 ml of a 5% sodium hydrogen carbonate solution. After stirring at ambient temperature for 1 hour and then settling out, the organic phase is separated and the aqueous phase is extracted with 25 ml of dichloromethane. The organic phases are combined, washed with saturated brine, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. 0.19 g of 4-fluoro-2-methylindole is thus obtained in the form of a dark red-colored oil, the characteristics of which are the following:

Workup

  1. stirringAfter stirring at ambient temperature for 1 hour
  2. customthe organic phase is separated
  3. extractionthe aqueous phase is extracted with 25 ml of dichloromethane
  4. washwashed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-c253a523f8ac4571a5dd02bdf407e1e4
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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