Sulfuric Acid → Ethyl (5-fluoro-2-methyl-1H-indol-3-yl)acetate

HRID 346806Notes

Reaction equation

HRID 346806 reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH2:5][CH2:6][C:7](=O)[CH3:8])[CH3:2].S(=O)(=O)(O)O.[F:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23]N)=[CH:19][CH:18]=1>C(O)C>[CH2:1]([O:3][C:4](=[O:10])[CH2:5][C:6]1[C:21]2[C:20](=[CH:19][CH:18]=[C:17]([F:16])[CH:22]=2)[NH:23][C:7]=1[CH3:8])[CH3:2]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 10883Ethyl levulinateHCID 69982(4-Fluorophenyl)hydrazine

Product 1

HCID 11665843Ethyl (5-fluoro-2-methyl-1H-indol-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4-Oxo-pentanoic acid ethyl ester (17.6 ml, 0.124 mol.) and conc. sulfuric acid (10 ml) were added to a solution of 4-fluorophenylhydrazine (20.2 g, 0.124 mol.) in abs. ethanol (90 ml), and the mixture was heated at reflux for 4 h. For working up, the mixture was filtered over silica gel and washed with ethanol (3×20 ml). The solution was poured into 500 ml of ice-water and extracted with ether (3×100 ml). The combined extracts were washed with 2M sodium hydrogen carbonate solution (50 ml), dried, filtered and concentrated. By recrystallisation from EE/cyclohexane (1:1) it was possible to obtain (5-fluoro-2-methyl-1H-indol-3-yl)acetic acid ethyl ester in a yield of 4.5 g (yellow solid, m.p. 61–62° C.).

Workup

  1. temperatureat reflux for 4 h
  2. filtrationthe mixture was filtered over silica gel
  3. washwashed with ethanol (3×20 ml)
  4. additionThe solution was poured into 500 ml of ice-water
  5. extractionextracted with ether (3×100 ml)
  6. washThe combined extracts were washed with 2M sodium hydrogen carbonate solution (50 ml)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customBy recrystallisation from EE/cyclohexane (1:1) it

Sources & evidence

ORD record
ord-c605ce638db04910bf951d4e592e843a
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Reaction notes

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