Dimethylformamide → 4-Bromo-2,6-difluorobenzaldehyde

HRID 1435058Notes

Reaction equation

HRID 1435058 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1.CN(C)[CH:24]=[O:25]>O1CCCC1.C(O)(=O)C>[Br:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([CH:24]=[O:25])=[C:16]([F:21])[CH:15]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 1363131-Bromo-3,5-difluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 27732904-Bromo-2,6-difluorobenzaldehydeYield 98.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of diisopropylamine (194.4 mmol) in tetrahydrofuran (350 mL) was cooled in an ice/water bath as n-BuLi (69.5 mL of a 2.5 M solution in hexanes) was added slowly via syringe. After 30 minutes, the solution was cooled in a dry ice/acetone bath as 1-bromo-3,5-difluorobenzene (173.7 mmol in 50 mL of tetrahydrofuran) was added gradually over the course of 25 minutes. After stirring for 30 minutes, dimethylformamide (208.4 mmol) was added gradually to the reaction mixture over the course of 30 minutes. After stirring for 2 hours more in the cooling bath, acetic acid (35 mL) was added, the cooling bath removed, and water (500 mL) was added. The reaction mixture was then extracted with ether (1 L), and the organic phase was washed with 1 N HCl (250 mL), brine, dried over magnesium sulfate and filtered. After condensing the organic phase with a rotary evaporator, the resulting brown solid was tritrated with hexanes before filtration to afford the title compound (I-1a) as a colorless solid (37.8 g).

Workup

  1. additionwas added slowly via syringe
  2. additionwas added gradually over the course of 25 minutes
  3. additionwas added
  4. customthe cooling bath removed
  5. additionwater (500 mL) was added
  6. extractionThe reaction mixture was then extracted with ether (1 L)
  7. washthe organic phase was washed with 1 N HCl (250 mL), brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customAfter condensing the organic phase
  11. customwith a rotary evaporator
  12. filtrationthe resulting brown solid was tritrated with hexanes before filtration

Sources & evidence

ORD record
ord-70a635f7d8904b7fb8f20ace1be5752e
Source dataset
uspto-grants-2009_11
Patent number
US07615651B2

Reaction notes

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