Benzyl Bromide → Indole-2-carboxylic acid, 1-benzyl-, ethyl ester

HRID 1392272Notes

Reaction equation

HRID 1392272 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 73125Ethyl indole-2-carboxylate

Product 1

HCID 140166Indole-2-carboxylic acid, 1-benzyl-, ethyl esterYield 85.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 1H-indole-2-carboxylic acid ethyl ester (1.89 g, 10.0 mmol) and benzylbromide (1.71 g, 10.0 mmol) in acetone (50 mL) was added cesium carbonate (3.26 g, 10.0 mmol). The mixture was heated to reflux overnight and then allowed to cool back to room temperature. The mixture was partitioned between ethyl acetate and brine and the layers were then separated. The aqueous layer was extracted with one additional portion of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel using ethyl acetate/hexanes (0/100 gradient to 6/94) to give 1-benzyl-1H-indole-2-carboxylic acid ethyl ester (2.38 g, 85%) as a white solid. 1H NMR (400 MHz, CDCl3); δ 7.68 (d, 1H), 7.37-7.11 (m, 7H), 7.02 (d, 2H), 5.82 (s, 2H), 4.30 (q, 2H), 1.33 (t, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. customThe mixture was partitioned between ethyl acetate and brine
  4. customthe layers were then separated
  5. extractionThe aqueous layer was extracted with one additional portion of ethyl acetate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by flash chromatography through silica gel

Sources & evidence

ORD record
ord-9c91af9e35504b93afabad01f2217606
Source dataset
uspto-grants-2008_03
Patent number
US07342039B2

Reaction notes

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