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

HRID 1776005

Reaction equation

HRID 1776005 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.[CH:10]12[CH2:16][CH:13]([CH:14]=[CH:15]1)[CH2:12][CH:11]2[CH:17]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([CH3:33])[CH:27]=1)[C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([CH3:25])[CH:19]=1.C(N(CC)CC)C.C(O)=O>C(OCC)(=O)C.CN(C=O)C>[OH:8][C:5]1[CH:6]=[CH:7][C:2]([CH:14]2[CH2:15][CH:10]3[CH2:16][CH:13]2[CH2:12][CH:11]3[CH:17]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([CH3:25])[CH:19]=2)[C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([CH3:33])[CH:27]=2)=[CH:3][C:4]=1[CH3:9]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 168964-Bromo-2-methylphenolHCID 676064534,4'(Bicyclo[2.2.1]hept-5-en-2-ylmethylene)bis(2-methylphenol)

Product 1

HCID 668356904,4'-((5-(4-Hydroxy-3-methylphenyl)bicyclo[2.2.1]heptan-2-yl)methylene)-bis(2-methylphenol)Yield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

Under a nitrogen atmosphere, 4-Bromo-2-methylphenol (4.69 g, 25.1 mmol), (tris-o-tolylphosphine)2PdCl2 (0.377 g; 0.480 mmol), and 4,4′-(bicyclo[2.2.1]hept-5-en-2-ylmethylene)bis(2-methylphenol) (5.14 g; 16.0 mmol) were charged to an appropriately sized and equipped reaction vessel. DMF (80 mL) was added to this reactant mixture to give a suspension. Triethylamine (11.0 mL, 78.9 mmol) and formic acid (2.30 mL, 60.9 mmol) were added to this suspension and then heated to 75° C. in an oil bath. The reaction mixture turned from its original orange suspension to pale yellow and became clear. During, the course of the reaction, the temperature of the reaction mixture rose to 82° C. and turned darker, and a gas evolved very slowly. Alter the initial exothermic reaction ceased, the reaction mixture was stirred overnight at 75° C. After this time, the reaction mixture was a clear, pale yellow solution with black particles. The cooled reaction mixture was diluted with ethyl acetate (80 mL) and washed with water (160 mL) to remove DMF. The organic layer was dried over anhydrous MgSO4. The crude mixture was purified by preparative TLC using a hexanes/ethyl acetate mixture (50:50) as developer to afford 3.7 g of 4,4′-((5-(4-hydroxy-3-methylphenyl)bicyclo[2.2.1]heptan-2-yl)methylene)-bis(2-methylphenol) (54% yield). The identity of the product as PP429 was confirmed by LC-MS (ESI) and proton NMR.

Workup

  1. customequipped
  2. customreaction vessel
  3. customto give a suspension
  4. customDuring, the course of the reaction
  5. customrose to 82° C.
  6. customexothermic reaction
  7. customThe cooled reaction mixture
  8. washwashed with water (160 mL)
  9. customto remove DMF
  10. dry with materialThe organic layer was dried over anhydrous MgSO4
  11. customThe crude mixture was purified by preparative TLC

Sources & evidence

ORD record
ord-70e5145b7e914f338c857eb5faef7b2d
Source dataset
uspto-grants-2016_02
Patent number
US09261781B2

Linked notes

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