N,N-Dimethylaniline → 2,6-dichloro-1H-indole

HRID 522750Notes

Reaction equation

HRID 522750 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=O)[NH:8]2)=[CH:4][CH:3]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:23]>C1(C)C=CC=CC=1>[Cl:23][C:7]1[NH:8][C:9]2[C:5]([CH:6]=1)=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 7363446-Chloro-1,3-dihydroindol-2-one

Product 1

HCID 217031202,6-dichloro-1H-indoleYield 63%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 6-chloroindolin-2-one 1 (500 mg, 2.99 mmol) in toluene (25 mL) under inert atmosphere were added N,N-dimethylaniline (362 mg, 2.99 mmol) and POCl3 (918 g, 5.98 mmol) at RT; heated to 110° C. and stirred for 1 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with 10% aq. NaHCO3 solution (30 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 5% EtOAc/Hexanes to afford compound 2 (350 mg, 63%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.09 (br s, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.28 (s, 1H), 7.09 (d, J=8.4 Hz, 1H), 6.39 (s, 1H); MS (ESI): m/z 184 (M−H+)

Workup

  1. customafter completion of the reaction
  2. customthe reaction mixture was quenched with 10% aq. NaHCO3 solution (30 mL)
  3. extractionextracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude
  8. customThis was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ca332013b0bb46c1a9314ba36ddcd0d8
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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