1,2-Dimethoxyethane → 4'-(Trifluoromethyl)-4-biphenylcarbaldehyde

HRID 1768324Notes

Reaction equation

HRID 1768324 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>CCCCCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([C:15]2[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 707414-BromobenzaldehydeHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 27827124'-(Trifluoromethyl)-4-biphenylcarbaldehyde

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8058HexaneSolvent

Procedure

A 3 L 3-neck flask fitted with top stirrer, condenser and argon inlet/outlet was charged with 4-trifluoromethybenzene boronic acid (90.0 g, 0.474 mol), 4-bromobenzaldehyde (83.29 g, 0.450 mol) and 1,2-dimethoxyethane (1.3 L), followed by 2M aqueous sodium carbonate (474 ml) and palladium acetate (5.32 g, 0.0237 mol). The stirring mixture was heated to reflux for 4 h under argon, then allowed to cool to room temperature over 16 h. The reaction mixture was filtered through hyflo. The filtrate was diluted with saturated brine and extracted 3× with ethyl acetate. The combined extracts were dried over magnesium sulfate and filtered through hyflo, giving a clear orange filtrate which was evaporated to a solid (ca. 120 g, crude). Flash chromatography (silica, 10–50% dichloromethane in pet. ether, 10% steps) gave a white solid which dissolved in hexane (500 ml) on boiling. Crystallisation, finally in ice, gave the title compound as a solid which was filtered off, washed with ice cold hexane and dried, (86.33 g, 77%). 1H-NMR (CDCl3) δ 7.77–8.03 (8H, m), 10.09 (1H, s).

Workup

  1. customA 3 L 3-neck flask fitted with top stirrer, condenser and argon inlet/outlet
  2. temperatureThe stirring mixture was heated
  3. temperatureto reflux for 4 h under argon
  4. filtrationThe reaction mixture was filtered through hyflo
  5. additionThe filtrate was diluted with saturated brine
  6. extractionextracted 3× with ethyl acetate
  7. dry with materialThe combined extracts were dried over magnesium sulfate
  8. filtrationfiltered through hyflo
  9. customgiving a clear orange filtrate which
  10. customwas evaporated to a solid (ca. 120 g, crude)
  11. customFlash chromatography (silica, 10–50% dichloromethane in pet. ether, 10% steps) gave a white solid which
  12. customCrystallisation

Sources & evidence

ORD record
ord-05c89cea9fc34ef3a9b96695b924a540
Source dataset
uspto-grants-2007_06
Patent number
US07235566B2

Reaction notes

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