4-Bromo-1H-indole-3-carbaldehyde → 4-Bromo-3-methyl-1H-indole

HRID 1159777Notes

Reaction equation

HRID 1159777 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[Br:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[C:10]([CH:17]=O)=[CH:11][NH:12]2>C1COCC1>[Br:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[C:10]([CH3:17])=[CH:11][NH:12]2

Participants

4

Reactant 2

HCID 27631784-Bromo-1H-indole-3-carbaldehyde2×HCID 21226445Aluminium lithium hydride

Product 1

HCID 529877044-Bromo-3-methyl-1H-indoleYield 92.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LAH (1.0M in THF, 5.75 mL, 5.75 mmol) was added dropwise to refluxing 4-bromo-1H-indole-3-carbaldehyde (644 mg, 2.87 mmol; Intermediate 27) in dry THF (20 mL). The mixture was refluxed 1 h, allowed to attain rt. and quenched with water (220 μL), W/w 15% aq. NaOH (220 μL) and water (650 μL). The resulting precipitation was filtered off, the filtrate concentrated and the residue was extracted with aq. NaOH (10 mL) and DCM (2×10 mL). The organic layers were combined with combined with an earlier batch of this intermediate (followed this experimental and starting from 4-bromo-1H-indole-3-carbaldehyde, 100 mg, 0.45 mmol; Intermediate 27), dried and concentrated to give the title compound (556 mg, 80%) as a light brown oil. MS (ESI+) for C9H8BrN m/z 210 (M+H)+.

Workup

  1. temperatureThe mixture was refluxed 1 h
  2. customto attain rt
  3. customand quenched with water (220 μL), W/w 15% aq. NaOH (220 μL) and water (650 μL)
  4. customThe resulting precipitation
  5. filtrationwas filtered off
  6. concentrationthe filtrate concentrated
  7. extractionthe residue was extracted with aq. NaOH (10 mL) and DCM (2×10 mL)
  8. dry with materialIntermediate 27), dried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-93ec121d0840423bbab25d5c676b2366
Source dataset
uspto-grants-2010_10
Patent number
US07812017B2

Reaction notes

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