1-Chloro-4-(chloromethyl)benzene → Ethyl 1-(4-chlorobenzyl)-1H-indole-2-carboxylate

HRID 2305579Notes

Reaction equation

HRID 2305579 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[H-].[Na+].[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1>CN(C=O)C>[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[C:2]2[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 73125Ethyl indole-2-carboxylate

Product 1

HCID 10519288Ethyl 1-(4-chlorobenzyl)-1H-indole-2-carboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl indole-2-carboxylate (0.5 g) was dissolved in DMF and sodium hydride (0.116 g) was added in a single portion. The reaction was stirred for 1 hour, then 4-chlorobenzyl chloride (0.468 g) was added dropwise. Stirring was continued for a further 2 hours and then the reaction was quenched by the addition of water. The reaction mixture was partitioned between water and ethyl acetate. Combined organic extracts were dried (MgSO4) and concentrated in vacuo and the residue purified by column chromatography using isohexane-5% ethyl acetate as eluent to give the desired end product as a white solid (0.61 g, 74%), mp 107-108°; NMR δ(CD3SOCD3) 1.25 (t, 3H), 4.3 (q, 2H), 5.8 (s, 2H), 7.1 (t, 1H), 7.3 (m, 4H), 7.55 (d, 1H), 7.7 (d, 1H); M/z (+) 314 (MH+).

Workup

  1. stirringStirring
  2. waitwas continued for a further 2 hours
  3. customthe reaction was quenched by the addition of water
  4. customThe reaction mixture was partitioned between water and ethyl acetate
  5. dry with materialCombined organic extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customthe residue purified by column chromatography

Sources & evidence

ORD record
ord-1ef09978b6334387952d4a877ca9d5b8
Source dataset
uspto-grants-2002_08
Patent number
US06441004B1

Reaction notes

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