Formic Acid → 4,4'-((5-(4-(5-(Bis(4-hydroxy-3-methylphenyl)methyl)bicyclo[2.2.1]heptan-2-yl)phenyl) bicyclo[2.2.1]heptan-2-yl)methylene)bis(2-methylphenol)

HRID 1776004Notes

Reaction equation

HRID 1776004 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[CH:9]12[CH2:15][CH:12]([CH:13]=[CH:14]1)[CH2:11][CH:10]2[CH:16]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH3:32])[CH:26]=1)[C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH3:24])[CH:18]=1.C(N([CH2:38][CH3:39])CC)C.[CH:40]([OH:42])=O.C([O:46][CH2:47][CH3:48])(=O)C>[Pd].CN(C=O)C>[OH:31][C:28]1[CH:29]=[CH:30][C:25]([CH:16]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH3:24])[CH:18]=2)[CH:10]2[CH2:11][CH:12]3[CH2:15][CH:9]2[CH2:14][CH:13]3[C:2]2[CH:7]=[CH:6][C:5]([CH:13]3[CH2:14][CH:9]4[CH2:15][CH:12]3[CH2:11][CH:10]4[CH:16]([C:25]3[CH:26]=[CH:27][C:40]([OH:42])=[C:38]([CH3:39])[CH:30]=3)[C:17]3[CH:22]=[CH:48][C:47]([OH:46])=[C:19]([CH3:20])[CH:18]=3)=[CH:4][CH:3]=2)=[CH:26][C:27]=1[CH3:32]

Participants

8

Reactant 5

HCID 284Formic AcidHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 12208p-DiiodobenzeneHCID 676064534,4'(Bicyclo[2.2.1]hept-5-en-2-ylmethylene)bis(2-methylphenol)

Product 1

HCID 668370994,4'-((5-(4-(5-(Bis(4-hydroxy-3-methylphenyl)methyl)bicyclo[2.2.1]heptan-2-yl)phenyl) bicyclo[2.2.1]heptan-2-yl)methylene)bis(2-methylphenol)Yield 60%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

1,4-Diiodobenzene (7.51 g, 22.8 mmol), (tris-o-tolylphosphine)2PdCl2 (0.713 g, 0.907 mmol), 4,4′(bicyclo[2.2.1]hept-5-en-2-ylmethylene)bis(2-methylphenol) (21.8 g; 68.0 mmol) and DMF (100 mL) were weighed and charged to an appropriately sized reaction vessel equipped with stirring and a reflux condenser and placed under a nitrogen atmosphere. Triethylamine (19.0 mL, 136 mmol) and formic acid (4.40 mL, 117 mmol) were then added with stirring to this mixture. The mixture was heated to 75° C. using an oil bath. During the course of heating the mixture changed from yellow to orange and became clear. The temperature of the reaction mixture rose to 119° C. due to the exotherm of the reaction and the solution became darker, with gas evolution. The reaction mixture was allowed to stir overnight (16 hours) at 75° C. in the oil bath. The reaction mixture obtained was a clear yellow solution with black palladium particles present. The reaction mixture was diluted with ethyl acetate (100 ml) and filtered through a silica gel plug. The filtrate was washed with water and the organic layer obtained was dried over anhydrous MgSO4. The crude mixture was purified with medium pressure column chromatography and the eluting solution was gradually changed from 100% hexanes to 100% ethyl acetate. This separation resulted in the isolation of 9.5 g of the PP719 (60% yield; 95% purity). The identity of the product was confirmed by as PP71.9 by LC-MS (ESI) and proton NMR.

Workup

  1. additioncharged to an appropriately sized reaction vessel
  2. customequipped
  3. customa reflux condenser and placed under a nitrogen atmosphere
  4. stirringwith stirring to this mixture
  5. temperatureDuring the course of heating the mixture
  6. customThe temperature of the reaction mixture rose to 119° C. due to the exotherm of the reaction
  7. stirringto stir overnight (16 hours) at 75° C. in the oil bath
  8. customThe reaction mixture obtained
  9. filtrationfiltered through a silica gel plug
  10. washThe filtrate was washed with water
  11. customthe organic layer obtained
  12. dry with materialwas dried over anhydrous MgSO4
  13. customThe crude mixture was purified with medium pressure column chromatography
  14. customThis separation
  15. customresulted in the isolation of 9.5 g of the PP719 (60% yield; 95% purity)

Sources & evidence

ORD record
ord-748f48749ae343cfbb533f9dcd08377b
Source dataset
uspto-grants-2016_02
Patent number
US09261781B2

Reaction notes

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