Iodine → HCID 86712326, compound

HRID 592449Notes

Reaction equation

HRID 592449 reaction equation
[C:1]1([C:7]2([C:11]([OH:13])=[O:12])[CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.II.C(O[I:20](C1C=CC=CC=1)OC(=O)C)(=O)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[I:20][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[C:7]1([C:11]([OH:13])=[O:12])[CH2:8][CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 807Iodine3×HCID 76724Iodobenzene diacetate3×HCID 2771711-Phenylcyclobutanecarboxylic acid

Product 1

HCID 86712326HCID 86712326, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1-phenyl-1-cyclobutanecarboxylic acid (2.00 g, 11.4 mmol) in DMF (10 mL) containing palladium (II) acetate (0.109 g, 0.567 mmol), iodine (2.16 g, 8.51 mmol) and (diacetoxyiodo)benzene (2.47 g, 8.51 mmol) was stirred at 60° C. for 18 hours in the absence of light. Additional iodine (2.16 g, 8.51 mmol) and (diacetoxyiodo)benzene (2.47 g, 8.51 mmol) were added and stirring was continued at 60° C. for 8 hours. A final addition of iodine (2.16 g, 8.51 mmol) and (diacetoxyiodo)benzene (2.47 g, 8.51 mmol) was performed and stirring was continued at 60° C. for 16 hours. The reaction mixture was partitioned between EtOAc and water and the aqueous phase was extracted several times with EtOAc. The combined organic fractions were washed with 10% sodium metabisulfate (3×30 mL), 10% citric acid (2×30 mL), water, brine, and then dried (MgSO4), filtered and the solvent evaporated. The crude product was dry loaded onto silica gel and the product was separated using silica column chromatography (Biotage Isolera, 40 g SiO2 Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A52 as a cream solid (425 mg, 12%). LCMS-A: rt 5.711 min.

Workup

  1. stirringstirring
  2. waitwas continued at 60° C. for 8 hours
  3. stirringstirring
  4. waitwas continued at 60° C. for 16 hours
  5. customThe reaction mixture was partitioned between EtOAc and water
  6. extractionthe aqueous phase was extracted several times with EtOAc
  7. washThe combined organic fractions were washed with 10% sodium metabisulfate (3×30 mL), 10% citric acid (2×30 mL), water, brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent evaporated
  11. dry with materialThe crude product was dry
  12. customthe product was separated
  13. customsilica column chromatography (Biotage Isolera, 40 g SiO2 Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-5c5d78fd6b2745cb92442f6b61dc5d26
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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