Bromine → 1-Benzyl-1h-indole-3-carboxylic acid (5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-methyl-amide

HRID 1357262Notes

Reaction equation

HRID 1357262 reaction equation
[Br:1]Br.[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([CH2:14][N:15]([CH3:34])[C:16]([C:18]1[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:19]=1)=[O:17])[CH:8]=[CH:7]2>C(O)(=O)C.C(OCC)(=O)C.C(O)(C)C>[Br:1][C:5]1[C:4]([OH:3])=[CH:13][CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9]([CH2:14][N:15]([CH3:34])[C:16]([C:18]1[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:19]=1)=[O:17])=[CH:10]2

Participants

6

Reactant 2

HCID 24408BromineHCID 865873871-benzyl-1H-indole-3-carboxylic acid (6-hydroxy-naphthalen-2-ylmethyl)-methyl-amide

Product 1

HCID 910261151-Benzyl-1h-indole-3-carboxylic acid (5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-methyl-amideYield 215.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of bromine (0.37 mL, 0.7134 mmol) in 60 mL glacial acetic acid was added dropwise under nitrogen over 2 h to a solution of 1-benzyl-1H-indole-3-carboxylic acid (6-hydroxy-naphthalen-2-ylmethyl)-methyl-amide (3.0 g, 0.713 mmol), prepared in the previous step, in 300 mL glacial acetic acid at room temperature. The reaction stirred for 18 h (overnight). The solvent was removed under reduced pressure. The resulting residue was diluted with ethyl acetate and extracted with 5% sodium bicarbonate. A solid precipitated from the organic layer and was collected by filtration. The filtrate was dried (MgSO4) and concentrated under reduced pressure to give a tan solid. The two solids were combined and taken up in a mixture of ethyl acetate and isopropanol. A certain amount of material (1.0 g) would not dissolve upon heating and was removed by filtration. The filtrate was allowed to cool and upon cooling crystals formed. The crystals were collected by filtration and dried under reduced pressure to give 1-benzyl-1H-indole-3-carboxylic acid (5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-methyl-amide (0.766 g, 22%) as a tan solid, mp 181-182° C.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionThe resulting residue was diluted with ethyl acetate
  3. extractionextracted with 5% sodium bicarbonate
  4. customA solid precipitated from the organic layer
  5. filtrationwas collected by filtration
  6. dry with materialThe filtrate was dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customto give a tan solid
  9. temperatureupon heating
  10. customwas removed by filtration
  11. temperatureto cool
  12. temperatureupon cooling crystals
  13. customformed
  14. filtrationThe crystals were collected by filtration
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-6ff3b1c90827477f9a638ca83452c824
Source dataset
uspto-grants-2003_07
Patent number
US06589970B2

Reaction notes

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