1-Bromo-2-fluoro-4-iodobenzene → HCID 86693060, compound

HRID 575027Notes

Reaction equation

HRID 575027 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[F:9].C([Mg]Cl)(C)C.[O:15]=[C:16]1[CH2:19][CH:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]1>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:16]2([OH:15])[CH2:17][CH:18]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:19]2)=[CH:4][C:3]=1[F:9]

Participants

5

Reactant 3

HCID 27250061-Bromo-2-fluoro-4-iodobenzeneHCID 10261520tert-Butyl 3-oxocyclobutanecarboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 86693060HCID 86693060, compoundYield 93.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 1-bromo-2-fluoro-4-iodobenzene (58 g, 192.76 mmol, 1.00 equiv) in tetrahydrofuran (600 mL), followed by the addition of i-PrMgCl (96.3 mL, 1.00 equiv) dropwise with stirring at 0° C. over 30 min. The mixture was stirred at 0° C. for 3 h. To this was added tert-butyl 3-oxocyclobutane-1-carboxylate (32.7 g, 192.12 mmol, 1.00 equiv) dropwise with stirring at −78° C. over 10 min. The mixture was stirred at −78 degree C. for 1 h and overnight at room temperature. The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. and extracted with 3×500 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 62 g (crude) of tert-butyl 3-(4-bromo-3-fluorophenyl)-3-hydroxycyclobutane-1-carboxylate as a yellow oil.

Workup

  1. customInto a 2000-mL 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe mixture was stirred at 0° C. for 3 h
  4. stirringwith stirring at −78° C. over 10 min
  5. stirringThe mixture was stirred at −78 degree C
  6. waitfor 1 h
  7. customovernight
  8. customat room temperature
  9. customThe reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C.
  10. extractionextracted with 3×500 mL of ethyl acetate
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-44699b683a514d51899bc41d43fc60ca
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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