Acetic Acid → Indole

HRID 1393330Notes

Reaction equation

HRID 1393330 reaction equation
Cl.FC(F)(F)O[C:5]1[CH:10]=[CH:9][C:8]([NH:11]N)=[CH:7][CH:6]=1.[C:15](O)(=O)[CH3:16]>>[NH:11]1[C:8]2[C:7](=[CH:6][CH:5]=[CH:10][CH:9]=2)[CH:16]=[CH:15]1

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 27773284-(Trifluoromethoxy)phenylhydrazine hydrochloride

Product 1

HCID 798Indole

Procedure

Ketone 2 (1.84 gr, 8.75 mmol) and 4-trifluoromethoxy phenylhydrazine hydrochloride (2.00 gr, 4.76 mmol) were stirred at 100° C. in acetic acid (40 ml, 0.22M) for 1 hour under nitrogen atmosphere to give a 1:2 mixture of 4- and 6-trifluoromethoxy indoles (desired 6-substituted indole is slightly less polar by TLC). The reaction was cooled to room temperature, the acetic acid was removed under reduced pressure and the residue was diluted with ethyl acetate and washed with water (1×) and brine (1×). The organic layer was dried with sodium sulfate, filtered and evaporated to afford 3 as a yellow oil after column chromatography (hexanes/ethyl acetate/1% acetic acid, 6:1); 1H-NMR (CDCl3, 500 MHz) δ 8.43 (br s, 1H), 8.16 (dd, 1H), 7.46 (d, 1H), 7.23 (t, 1H), 7.14 (t, 1H), 7.03 (d, 1H), 6.74 (d, 1H), 2.54 (s, 3H).

Workup

  1. customto give
  2. customthe acetic acid was removed under reduced pressure
  3. additionthe residue was diluted with ethyl acetate
  4. washwashed with water (1×) and brine (1×)
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-a7de6e008e7c4ebd929f34de2aa62677
Source dataset
uspto-grants-2008_03
Patent number
US07345085B2

Reaction notes

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