Pyridine → 7-bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indole

HRID 2421230Notes

Reaction equation

HRID 2421230 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:19])[C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[F:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][C:26]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.N1C=CC=CC=1.B(O)O>ClCCl.C(OCC)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([F:19])[C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:6]2[C:10]=1[N:9]([C:23]1[CH:24]=[CH:25][C:26]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[C:21]([F:20])[CH:22]=1)[CH:8]=[CH:7]2

Participants

8

Reactant 4

HCID 1049Pyridine2×HCID 61668Boronic Acid2×HCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 583038564-(benzyloxy)-7-bromo-5-fluoro-1H-indole

Product 1

HCID 596279357-bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indoleYield 30%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-bromo-5-fluoro-4-[(phenylmethyl)oxy]-1H-indole (D5) (3 g, 9.37 mmol), {3-fluoro-4-[(phenylmethyl)oxy]phenyl}boronic acid (3.46 g, 14.06 mmol), copper (II) acetate (2.55 g, 14.06 mmol) and pyridine (0.834 mL, 0.815 g, 10.31 mmol) in dichloromethane (50 mL) were stirred together vigorously under an air atmosphere with powdered 4A molecular sieves (˜10 g). After stirring for 20 hours, another 0.5 g of boronic acid were added and the mixture was stirred for a further 24 hours. Then another 1.73 g boronic acid (0.75 eq), copper acetate (1.28 g, 0.75 eq) and pyridine (1.52 mL, 2 eq) were added and stirring was continued at room temperature. After a further 24 hours, the reaction was diluted with ethyl acetate and filtered through celite. The celite was washed with ethyl acetate and the combined filtrates were washed with water (2×), dried (Na2SO4) and concentrated. Chromatography SP4 (0-30% ethyl acetate in hexane) gave the title compound as a white solid (D6), (1.463 g).

Workup

  1. stirringthe mixture was stirred for a further 24 hours
  2. stirringstirring
  3. customwas continued at room temperature
  4. waitAfter a further 24 hours
  5. filtrationfiltered through celite
  6. washThe celite was washed with ethyl acetate
  7. washthe combined filtrates were washed with water (2×)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-09c761198be24bf9a6dd5fea6443048a
Source dataset
uspto-grants-2011_06
Patent number
US07956083B2

Reaction notes

Loading…