Ammonium Hydroxide → 4-Methoxy-7-cyanoindole

HRID 1368166Notes

Reaction equation

HRID 1368166 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9](Br)=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2.[C:13]([Cu])#[N:14].[OH-].[NH4+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([C:13]#[N:14])=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 36954997-Bromo-4-methoxy-1H-indoleHCID 178418546HCID 178418546, compound

Product 1

HCID 226330844-Methoxy-7-cyanoindole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
165 °C

Procedure

To an oven dried 500 ml round bottom flask at rt. was charged with 4-methoxy-7-bromo-indole intermediate 5 (12.8 g, 56.6 mmol) and dry DMF (120 ml), followed by CuCN (25.3 g, 283 mmol). The reaction mixture was refluxed at 165° C. for 16 hr. After cooling to rt., the mixture was slowly added ammonium hydroxide (100 ml), stirred for 10 min, concentrated in vacuo to ˜50 ml and diluted with CHCl3 (250 ml). The organic mixture was washed with H2O (250 ml), and the aqueous layer back extracted with CHCl3 (2×200 ml). The combined organic extracts were filtered through a filter paper to remove some solids, and washed again with H2O (100 ml) and brine (100 ml), and then dried (MgSO4). After evaporation in vacuo, the residue was purified by flash column chromatography (10% EtOAc/Hexane (250 ml), then 25% EtOAc/Hexanes (1250 ml)) to afford 4-methoxy-7-cyanoindole intermediate 35 (8.0 g, 82%) as yellow solids. 1H NMR: (CDCl3) δ 8.73 (b s, 1H), 7.50 (d, J=8.3 Hz), 7.22 (app t, J=2.8 Hz, 1H), 6.73 (dd, J=2.3, 3.2 Hz, 1H), 6.58 (d, J=8.3 Hz, 1H), 4.01 (s, 3H); LC/MS: (ES+) m/z (M+H)+=173, HPLC (YMC C18 S7 3×50 mm, Flow Rate 4 ml/min, Gradient Time 3 min) Rt=1.700.

Workup

  1. customTo an oven dried 500 ml round bottom flask at rt
  2. temperatureAfter cooling to rt
  3. concentrationconcentrated in vacuo to ˜50 ml
  4. additiondiluted with CHCl3 (250 ml)
  5. washThe organic mixture was washed with H2O (250 ml)
  6. extractionthe aqueous layer back extracted with CHCl3 (2×200 ml)
  7. filtrationThe combined organic extracts were filtered through a filter paper
  8. customto remove some solids
  9. washwashed again with H2O (100 ml) and brine (100 ml)
  10. dry with materialdried (MgSO4)
  11. customAfter evaporation in vacuo
  12. customthe residue was purified by flash column chromatography (10% EtOAc/Hexane (250 ml)

Sources & evidence

ORD record
ord-eec2410596554307b2c30747acf05a09
Source dataset
uspto-grants-2003_06
Patent number
US06573262B2

Reaction notes

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