Tetrahydrofuran → 2,6-Diethoxy-4'-fluoro-biphenyl-4-carbaldehyde

HRID 531045Notes

Reaction equation

HRID 531045 reaction equation
C1COCC1.[CH2:6]([O:8][C:9]1[CH:14]=[C:13]([C:15](OCC)=[O:16])[CH:12]=[C:11]([O:20][CH2:21][CH3:22])[C:10]=1[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH3:7].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O>[CH2:6]([O:8][C:9]1[CH:14]=[C:13]([CH:15]=[O:16])[CH:12]=[C:11]([O:20][CH2:21][CH3:22])[C:10]=1[C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)[CH3:7]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 66644576Ethyl 2,6-diethoxy-4'-fluorobiphenyl-4-carboxylate

Product 1

HCID 593831002,6-Diethoxy-4'-fluoro-biphenyl-4-carbaldehydeYield 83.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A THF (200 mL) solution of ethyl 2,6-diethoxy-4′-fluorobiphenyl-4-carboxylate (50.7 g) was added to a THF (200 mL) suspension of lithium aluminum hydride (4.34 g) under ice cooling. After stirring at the same temperature as above for 30 minutes, water (4.5 mL) and a 1 M aqueous sodium hydroxide solution (4.5 mL) were added thereto, and the mixture was stirred for 5 minutes. Water (13.5 mL) was further added thereto. The reaction mixture was stirred for 1 hour and then filtered through celite, and the filtrate was concentrated under reduced pressure. A sulfur trioxide-pyridine complex (48.6 g) was added to a DMSO (250 mL) solution of the obtained residue and triethylamine (63.8 mL), and the mixture was stirred at room temperature for 30 minutes. Water (450 mL) was added to the reaction mixture, and the deposited solid was collected by filtration. The obtained solid was recrystallized (ethanol/water) to obtain the title compound (36.9 g).

Workup

  1. stirringThe reaction mixture was stirred for 1 hour
  2. filtrationfiltered through celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionA sulfur trioxide-pyridine complex (48.6 g) was added to a DMSO (250 mL) solution of the obtained residue and triethylamine (63.8 mL)
  5. stirringthe mixture was stirred at room temperature for 30 minutes
  6. additionWater (450 mL) was added to the reaction mixture
  7. filtrationthe deposited solid was collected by filtration
  8. customThe obtained solid was recrystallized (ethanol/water)

Sources & evidence

ORD record
ord-3174a62b5b25491db9ca84e77e8133c9
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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