Benzyl Chloride → 2-cyclopropyl-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetic acid methyl ester

HRID 1069643Notes

Reaction equation

HRID 1069643 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH3:15])[CH:12]=2)[NH:7][C:6]=1[CH:16]1[CH2:18][CH2:17]1.[H-].[Na+].[CH2:22](Cl)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:19])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH3:15])[CH:12]=2)[N:7]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:6]=1[CH:16]1[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 107537632-cyclopropyl-5-methoxyl-1H-indole-3-acetic acid methyl ester

Product 1

HCID 108316472-cyclopropyl-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetic acid methyl esterYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3.8 g (146 mmol) of 2-cyclopropyl-5-methoxyl-1H-indole-3-acetic acid methyl ester in 50 mL of DMF was treated with 0.59 g (0146 mol) of 60% NaH/mineral oil, stirred 0.5 hour, and 1.69 mL (146 mmol) of benzyl chloride added. After 20 hours, the reaction mixture was diluted with water, extracted with EtOAc, the EtOAc solution was washed four times with water and dried over Na2SO4. After concentrating at reduced pressure, the product was purified by chromatography on silica, eluting with a gradient, 5% EtOAc/toluene→15% EtOAc/toluene, to give 2.05 g (40% yield) of 2-cyclopropyl-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetic acid methyl ester as an oil.

Workup

  1. waitAfter 20 hours
  2. extractionextracted with EtOAc
  3. washthe EtOAc solution was washed four times with water
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrating at reduced pressure
  6. customthe product was purified by chromatography on silica
  7. washeluting with a gradient, 5% EtOAc/toluene→15% EtOAc/toluene

Sources & evidence

ORD record
ord-40c8e0ce106f4ad480584aaba4f80c2c
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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