Indole → 1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indole

HRID 244474

Reaction equation

HRID 244474 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].Cl[CH2:13][CH:14]1[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[O:15]1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:19][C:16]1([CH3:20])[O:15][CH:14]([CH2:13][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[CH2:18][O:17]1

Participants

6

Reactant 3

HCID 798IndoleHCID 203744-(Chloromethyl)-2,2-dimethyl-1,3-dioxolane2×HCID 24758Sodium hydride

Product 1

HCID 594373201-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indoleYield 28.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred room temperature solution of indole (5.9 g, 50 mmol) in THF (100 mL) was added sodium hydride (2.4 g of 60% in mineral oil, 60 mmol) in one portion. After 30 minutes, 4-chloromethyl-2,2-dimethyl-1,3-dioxolane (10.6 mL, 75 mmol) was added followed by tetra-n-butylammonium iodide (1.9 g, 5 mmol) and the mixture was warmed at reflux. After 24 hours, LCMS showed about 50% conversion [MS m/z 232 (MH+)]. Additional 4-chloromethyl-2,2-dimethyl-1,3-dioxolane (11.4 mL) was added and the refluxing continued. After 18 hours, the mixture was cooled, diluted with THF (300 mL), filtered, and concentrated in vacuo to afford a brown oil. The residue was purified by column chromatography over silica gel eluting with 0-100% methylene chloride in hexanes and the product-rich fractions were collected to afford 3.3 g of 1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indole as a brownish oil.

Workup

  1. temperaturethe mixture was warmed
  2. temperatureat reflux
  3. waitAfter 24 hours
  4. waitAfter 18 hours
  5. temperaturethe mixture was cooled
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a brown oil
  9. customThe residue was purified by column chromatography over silica gel eluting with 0-100% methylene chloride in hexanes
  10. customthe product-rich fractions were collected

Sources & evidence

ORD record
ord-c94e943c02ee4d41a5c763313e158079
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Linked notes

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