Triethylamine → 7-Chloro-1-(3-fluoro-4-methoxyphenyl)-4-methoxy-1H-indole

HRID 2421236Notes

Reaction equation

HRID 2421236 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[F:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][C:19]=1[O:20][CH3:21].C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]2[C:10]=1[N:9]([C:16]1[CH:17]=[CH:18][C:19]([O:20][CH3:21])=[C:14]([F:13])[CH:15]=1)[CH:8]=[CH:7]2

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 27821943-Fluoro-4-methoxyphenylboronic acid2×HCID 53399269HCID 53399269, compound

Product 1

HCID 596279267-Chloro-1-(3-fluoro-4-methoxyphenyl)-4-methoxy-1H-indoleYield 22.7%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-chloro-4-(methyloxy)-1H-indole (D11) (1.15 g, 6.35 mmol) in dichloromethane (20 mL) was added 3-fluoro-4-methoxyphenylboronic acid (2.2 g, 12.9 mmol), triethylamine (1.8 mL, 12.9 mmol), copper (II) acetate (2.3 g, 12.7 mmol) and powdered 4A molecular sieves (2.0 g). The reaction mixture was stirred at room temperature in the presence of air for 3 days. Further quantities of 3-fluoro-4-methoxyphenylboronic acid (440 mg), triethylamine (0.36 mL) and copper acetate (440 mg) were added and the mixture stirred at room temperature in the presence of air for a further 16 hours. The mixture was filtered and the solid washed with dichloromethane. The filtrate was concentrated at reduced pressure. The product was partially purified by silica gel chromatography eluting with 2-35% dichloromethane in hexane. The resulting product was partially dissolved in dimethylsulphoxide and acetonitrile. The undissolved solid was collected by filtration to yield the title compound (D12) (440 mg). The filtrate was concentrated at reduced pressure and the product purified by MDAP to yield a further batch of the title compound (D12), (143 mg).

Workup

  1. stirringthe mixture stirred at room temperature in the presence of air for a further 16 hours
  2. filtrationThe mixture was filtered
  3. washthe solid washed with dichloromethane
  4. concentrationThe filtrate was concentrated at reduced pressure
  5. customThe product was partially purified by silica gel chromatography
  6. washeluting with 2-35% dichloromethane in hexane
  7. dissolutionThe resulting product was partially dissolved in dimethylsulphoxide
  8. filtrationThe undissolved solid was collected by filtration

Sources & evidence

ORD record
ord-68eec03cc7c940daa70b942bff561834
Source dataset
uspto-grants-2011_06
Patent number
US07956083B2

Reaction notes

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