Indole → 2-[3-(1H-Indol-3-ylmethyl)-phenoxymethyl]-quinoline

HRID 892212Notes

Reaction equation

HRID 892212 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([Mg]Br)C.Cl.Cl[CH2:16][C:17]1[CH:18]=[C:19]([CH:32]=[CH:33][CH:34]=1)[O:20][CH2:21][C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=1.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:16][C:17]2[CH:18]=[C:19]([CH:32]=[CH:33][CH:34]=2)[O:20][CH2:21][C:22]2[CH:31]=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)=[CH:2]1

Participants

7

Reactant 4

HCID 798IndoleHCID 516892Sodium BicarbonateHCID 145017072-(3-Chloromethylphenoxymethyl)quinoline hydrochlorideHCID 178418443HCID 178418443, compound

Product 1

HCID 222415112-[3-(1H-Indol-3-ylmethyl)-phenoxymethyl]-quinoline

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Indole (230 mg, 2.0 mmol) is dissolved in tetrahydrofuran (3 mL) and ethylmagnesium bromide (1 M, 2.0 mL, 2.0 mmol) is added and the reaction is heated for 2 h at 65° C. The free base of 2-(3-chloromethyl-phenoxymethyl)-quinoline hydrochloride (400 mg, 1.2 mmol, example 49) is prepard by partioning the material between ethyl ether and sodium bicarbonate and drying the organic phase with magnesium sulfate. This free base is dissolved in tetrahydrofuran (2 mL) and is added to the cooled indole/Grignard solution, along with catalytic tetrabutylammonium iodide. This mixture is heated 6 h at 65° C. The reaction is then cooled and partitioned between ethyl ether and ammonium chloride. The organic phase is washed with brine, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, dichloromethane) to yield the title compound. MS (ESI) 365 (M+H)+.

Workup

  1. dry with materialdrying the organic phase with magnesium sulfate
  2. dissolutionThis free base is dissolved in tetrahydrofuran (2 mL)
  3. additionis added to the cooled indole/Grignard solution, along with catalytic tetrabutylammonium iodide
  4. temperatureThis mixture is heated 6 h at 65° C
  5. temperatureThe reaction is then cooled
  6. custompartitioned between ethyl ether and ammonium chloride
  7. washThe organic phase is washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. custompurified by column chromatography (silica, dichloromethane)

Sources & evidence

ORD record
ord-39f0aefe824e4dfe8873acb09fb372f0
Source dataset
uspto-grants-2006_02
Patent number
US07005440B1

Reaction notes

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