Sodium hydride → Ethyl N-[(4-chloro-3-iodophenyl)methyl]-5-acetoxyindole-2-carboxylate

HRID 1610931Notes

Reaction equation

HRID 1610931 reaction equation
[H-].[Na+].[C:3]([O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10]2)(=[O:5])[CH3:4].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][C:23]=1[I:30]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.[Cl-].[NH4+]>[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][N:12]2[C:13]3[C:9](=[CH:8][C:7]([O:6][C:3](=[O:5])[CH3:4])=[CH:15][CH:14]=3)[CH:10]=[C:11]2[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:24][C:23]=1[I:30]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 11379620Ethyl 5-acetoxyindole-2-carboxylateHCID 156895474-(Bromomethyl)-1-chloro-2-iodobenzene

Product 1

HCID 22259365Ethyl N-[(4-chloro-3-iodophenyl)methyl]-5-acetoxyindole-2-carboxylateYield 8.1%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×HCID 25517Ammonium ChlorideSolvent2×

Procedure

Sodium hydride (0.23 g of a 60% dispersion in oil) was added to a solution of ethyl 5-acetoxyindole-2 carboxylate (1.29 g) and tetra-n-butylammonium iodide (10 mg) in anhydrous DMF (25 ml) under a stream of argon. The reaction mixture was stirred for 15 minutes and a solution of 4-chloro-3-iodobenzyl bromide (1.9 g) in DMF (5 ml) was added. The mixture was stirred for 15 hours, then saturated aq. ammonium chloride (5 ml) was added. The residue obtained on removal of the solvent was diluted with saturated aq. ammonium chloride (50 ml) and extracted with ethyl actate (3×30 ml). The combined ethyl acetate extracts were washed with brine (100 ml) and dried. The residue obtained on removal of the solvent was purified by chromatography on silica eluting with a mixture of ethyl acetate and iso-hexane (1:9) to give the title compound (0.21 g). NMR (CD3SOCD3): d 1.1 (t, 3H), 2.2 (s, 3H), 4.3 (m, 2H), 5.8 (s, 2H), 6.9 (m, 1H), 7.1 (m, 1H), 7.35 (m, 1H), 7.4 (m, 2H), 7.6 (m 2H), 7.7 (m, 2H); m/z 497.5 (M+H).

Workup

  1. stirringThe mixture was stirred for 15 hours
  2. customThe residue obtained on removal of the solvent
  3. extractionextracted with ethyl actate (3×30 ml)
  4. washThe combined ethyl acetate extracts were washed with brine (100 ml)
  5. customdried
  6. customThe residue obtained on removal of the solvent
  7. customwas purified by chromatography on silica eluting with a mixture of ethyl acetate and iso-hexane (1:9)

Sources & evidence

ORD record
ord-35e56954948545e08a589f7a9b3e3059
Source dataset
uspto-grants-2006_01
Patent number
US06984657B1

Reaction notes

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