Water → Methyl 5-fluoro-1H-indole-3-carboxylate

HRID 888911Notes

Reaction equation

HRID 888911 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.FC(F)(F)[C:13]([O:15][C:16](=O)C(F)(F)F)=[O:14].O>CN(C=O)C>[CH3:16][O:15][C:13]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)[NH:7][CH:6]=1)=[O:14]

Participants

5

Reactant 3

HCID 962WaterHCID 9845Trifluoroacetic anhydrideHCID 678615-Fluoroindole

Product 1

HCID 34176452Methyl 5-fluoro-1H-indole-3-carboxylateYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-fluoroindole (5 g, 37.0 mmol) in DMF (40 mL) was treated at 0° C. with trifluoroacetic anhydride (6.1 mL, 42.6 mmol). After 30 min, the reaction was poured into water and the resulting precipitate collected by filtration, washed with water, then dried in vacuo. The solid was then dissolved in 10% aqueous NaOH (200 mL) and heated at reflux for 1 h. The reaction mixture was then cooled, washed with dichloromethane and acidified with aqueous HCl. The resulting white precipitate was collected by filtration, washed with water, taken up in dichloromethane, washed with water, dried (MgSO4) and evaporated in vacuo. The resulting material (5 g, 75%) was dissolved in methanol (80 mL) and treated with concentrated sulphuric acid (2 mL) then heated at reflux overnight. The reaction was cooled and the resulting precipitate collected, washed with water and evaporated in vacuo to give 5-fluoro-1H-indole-3-carboxylic acid methyl ester as a peach-coloured solid (4.5 g, 83%).

Workup

  1. filtrationthe resulting precipitate collected by filtration
  2. washwashed with water
  3. customdried in vacuo
  4. dissolutionThe solid was then dissolved in 10% aqueous NaOH (200 mL)
  5. temperatureheated
  6. temperatureat reflux for 1 h
  7. temperatureThe reaction mixture was then cooled
  8. washwashed with dichloromethane
  9. filtrationThe resulting white precipitate was collected by filtration
  10. washwashed with water
  11. washwashed with water
  12. dry with materialdried (MgSO4)
  13. customevaporated in vacuo
  14. dissolutionThe resulting material (5 g, 75%) was dissolved in methanol (80 mL)
  15. additiontreated with concentrated sulphuric acid (2 mL)
  16. temperaturethen heated
  17. temperatureat reflux overnight
  18. temperatureThe reaction was cooled
  19. customthe resulting precipitate collected
  20. washwashed with water
  21. customevaporated in vacuo

Sources & evidence

ORD record
ord-55bef237fcba4c5aad862f7ea09d0f45
Source dataset
uspto-grants-2012_08
Patent number
US08252792B2

Reaction notes

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