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

HRID 2421231Notes

Reaction equation

HRID 2421231 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:34])[C:5]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:6]2[C:10]=1[N:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:13]([F:25])[CH:12]=1)[CH:8]=[CH:7]2.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1.CC(N=NC(C#N)(C)C)(C#N)C>[F:34][C:4]1[C:5]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[C:6]2[C:10](=[CH:2][CH:3]=1)[N:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:13]([F:25])[CH:12]=1)[CH:8]=[CH:7]2

Participants

6

Reactant 3

HCID 5948Tributylstannane4×HCID 6547Azobisisobutyronitrile3×HCID 596279357-bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indole

Product 1

HCID 596279345-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indoleYield 42.1%

Reagents, catalysts & solvents 2

HCID 6547AzobisisobutyronitrileCatalystHCID 1140TolueneSolvent

Procedure

A solution of 7-bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indole (D6) (400 mg, 0.769 mmol) in toluene (10 mL) was degassed by bubbling Argon through for a few minutes and tributylstannane (0.248 mL, 0.922 mmol) was added. The mixture was heated to reflux under argon and AIBN (˜5 mg) was added and refluxing was continued. After 6 hours, another 0.124 mL of Bu3SnH and a few crystals of AIBN were added and the mixture refluxed overnight—only a small amount of further reaction occurred therefore another 0.124 mL of Bu3SnH and a few crystals of AIBN added and refluxing continued, again further reaction occurred but then stopped. Further quantities of Bu3SnH (4×0.124 mL) together with a few crystals of AIBN were added at approx 2 hourly intervals. It was noticed that the reaction proceeded much more with thorough degassing with argon prior to addition of Bu3SnH. After completion of the reaction (˜48 hours total reaction), the toluene was evaporated and ether/20% aqueous ammonia were added. The product was extracted into ether and the extracts were washed with 20% aqueous ammonia (3×). The ether layer was dried over Na2SO4 and concentrated and the product was triturated with hexane to remove high Rf impurities. Chromatography on silica gel (elution with 0-15% diethyl ether in hexane) gave the title compound as a clear gum (D7), (143 mg).

Workup

  1. additionwas added
  2. temperatureThe mixture was heated
  3. temperatureto reflux under argon
  4. temperaturerefluxing
  5. temperaturethe mixture refluxed overnight—only
  6. customa small amount of further reaction
  7. temperaturerefluxing
  8. customagain further reaction
  9. customwith thorough degassing with argon
  10. additionto addition of Bu3SnH
  11. customAfter completion of the reaction (˜48 hours total reaction)
  12. customthe toluene was evaporated
  13. additionether/20% aqueous ammonia were added
  14. extractionThe product was extracted into ether
  15. washthe extracts were washed with 20% aqueous ammonia (3×)
  16. dry with materialThe ether layer was dried over Na2SO4
  17. concentrationconcentrated
  18. customthe product was triturated with hexane
  19. customto remove high Rf impurities

Sources & evidence

ORD record
ord-111267dc5b9a49eea445af68cc2fd0c0
Source dataset
uspto-grants-2011_06
Patent number
US07956083B2

Reaction notes

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