Pyridine → 7-Bromo-5-fluoro-3-(3-fluoro-benzyl)-benzofuran-2-sulfonyl chloride

HRID 18191

Reaction equation

HRID 18191 reaction equation
[Br:1][C:2]1[C:10]2[O:9][CH:8]=[C:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[C:6]=2[CH:5]=[C:4]([F:19])[CH:3]=1.BrC1C=C(F)C=CC=1O.FC1C=C(C=CC=1)C=CC=O.[Cl:40][S:41](O)(=[O:43])=[O:42].N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl>ClCCl.O>[Br:1][C:2]1[C:10]2[O:9][C:8]([S:41]([Cl:40])(=[O:43])=[O:42])=[C:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[C:6]=2[CH:5]=[C:4]([F:19])[CH:3]=1

Participants

9

Reactant 6

HCID 1049PyridineHCID 24638Chlorosulfonic acidHCID 24819Phosphorus pentachlorideHCID 6054722-Bromo-4-fluorophenolHCID 534011243-FluorocinnamaldehydeHCID 593449097-Bromo-5-fluoro-3-(3-fluoro-benzyl)-benzofuran

Product 1

HCID 593449227-Bromo-5-fluoro-3-(3-fluoro-benzyl)-benzofuran-2-sulfonyl chloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-15 °C

Procedure

7-Bromo-5-fluoro-3-(3-fluoro-benzyl)-benzofuran (0.97 gm, 3.0 mmol, prepared from 2-bromo-4-fluoro-phenol and 3-fluoro-cinnamaldehyde following the procedure of steps 1 and 2 of Example 8) was dissolved in dichloromethane (30 ml) and chilled to −15° C. Chlorosulfonic acid (0.26 ml, 3.9 mmol) in dichloromethane (2 ml) was added in portions, and the reaction mixture was stirred for 10 minutes then warmed to room temperature and stirred for 16 hours. To the resulting slurry was added pyridine (0.33 ml, 4.08 mmol) and phosphorus pentachloride (0.812 gm, 3.9 mmol) and the reaction mixture was stirred for 24 hours. Water was added and the reaction mixture was stirred for 30 minutes. The organic layer was separated, dried over magnesium sulfate, dried onto silica gel, and layered over a pad of silica gel in a fritted funnel. The silica gel was eluted with ethyl acetate/hexanes (1/9) to give 7-bromo-5-fluoro-3-(3-fluoro-benzyl)-benzofuran-2-sulfonyl chloride.

Workup

  1. temperaturethen warmed to room temperature
  2. stirringstirred for 16 hours
  3. stirringthe reaction mixture was stirred for 24 hours
  4. stirringthe reaction mixture was stirred for 30 minutes
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. customdried onto silica gel
  8. customlayered over a pad of silica gel in a fritted funnel
  9. washThe silica gel was eluted with ethyl acetate/hexanes (1/9)

Sources & evidence

ORD record
ord-cbd6c6f9821a4cfebfb307000c188252
Source dataset
uspto-grants-2010_06
Patent number
US07741326B2

Linked notes

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