Hydrochloric Acid → 2,2,2-trichloro-1-(6-chloro-5-(4-ethoxyphenyl)-1H-indol-3-yl)ethanone

HRID 1054647Notes

Reaction equation

HRID 1054647 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=1.N1C=CC=CC=1.[Cl:26][C:27]([Cl:32])([Cl:31])[C:28](Cl)=[O:29].Cl>C1COCC1>[Cl:26][C:27]([Cl:32])([Cl:31])[C:28]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([Cl:1])=[C:3]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=3)[CH:4]=2)[NH:8][CH:7]=1)=[O:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6420Trichloroacetyl chlorideHCID 866986496-Chloro-5-(4-ethoxyphenyl)-1H-indole

Product 1

HCID 866986512,2,2-trichloro-1-(6-chloro-5-(4-ethoxyphenyl)-1H-indol-3-yl)ethanoneYield 9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-chloro-5-(4-ethoxyphenyl)-1H-indole (500.0 mg, 1.84 mmol) in anhydrous THF (5 mL) was added pyridine (436.0 mg, 5.52 mmol) and trichloroacetyl chloride (10 mL) at 0° C. under N2. The reaction mixture was stirred at room temperature under N2 for 12 hours. The mixture was poured into 0.5 N HCl (200 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (9-25% EtOAc/petroleum ether:EtOAc) to give the title compound (70.0 mg, 9%) as a green solid. 1H NMR (400 MHz, CDCl3) δ 8.80 (br, 1 H), 8.40 (s, 1 H), 8.36 (d, J=3.2 Hz, 1 H), 7.59 (s, 1 H), 7.42 (d, 2H), 6.97 (d, 2 H), 4.12 (q, J=7.00 Hz, 2 H), 1.45 (t, J=7.00 Hz, 3 H).

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined organic layers were washed with brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (9-25% EtOAc/petroleum ether:EtOAc)

Sources & evidence

ORD record
ord-42ce0111987e44a28091af437bc21fb9
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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