Chloroacetonitrile → 4-bromo-1-cyanomethyl-1H-indole-2-carboxylic acid ethyl ester

HRID 853041Notes

Reaction equation

HRID 853041 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[C:14]([Br:17])[CH:13]=[CH:12][CH:11]=2)=[O:7])[CH3:4].Cl[CH2:19][C:20]#[N:21]>CN(C)C=O>[CH2:3]([O:5][C:6]([C:8]1[N:9]([CH2:19][C:20]#[N:21])[C:10]2[C:15]([CH:16]=1)=[C:14]([Br:17])[CH:13]=[CH:12][CH:11]=2)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 10989255Ethyl 4-bromo-1H-indole-2-carboxylate

Product 1

HCID 694154234-bromo-1-cyanomethyl-1H-indole-2-carboxylic acid ethyl esterYield 71.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodiumhydride (4.0 g, 92 mmol) was suspended in dimethylformamide (20 mL) and a solution of 4-bromo-1H-Indole-2-carboxylic acid ethyl ester (16.4 g, 61 mmol) in dimethylformamide (70 mL) was added. The mixture was stirred for 1 h at room temperature and after cooling to 0° C. chloroacetonitrile (7.7 mL, 122 mmol) was added. After 1 h at room temperature the mixture was added to an ice/water mixture (800 mL) and extracted with ethylacetate. The organic phases were pooled washed with brine, dried with MgSO4 and the solvent was removed in vacuo. Chromatography on silica gel (ethyl acetate/n-hexane 4:1) yielded 4-bromo-1-cyanomethyl-1H-indole-2-carboxylic acid ethyl ester (13.4 g, 71%) as a colorless solid, MS: m/e=306.0 (M+).

Workup

  1. additionwas added
  2. extractionextracted with ethylacetate
  3. washThe organic phases were pooled washed with brine
  4. dry with materialdried with MgSO4
  5. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-0a56b83faa7d46ebbfa9f9a3fa37c3d6
Source dataset
uspto-grants-2007_08
Patent number
US07253281B2

Reaction notes

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