Dimethylformamide → 3-Bromo-5-[(4-fluorophenyl)hydroxymethyl]benzaldehyde

HRID 53325

Reaction equation

HRID 53325 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[C:11](Br)[CH:10]=[C:9]([Br:14])[CH:8]=1.[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1.CN(C)[CH:26]=[O:27]>CCCCCC.C(OCC)C.O>[Br:14][C:9]1[CH:10]=[C:11]([CH:12]=[C:7]([CH:20]([C:19]2[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=2)[OH:21])[CH:8]=1)[CH:26]=[O:27]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 122791,3,5-TribromobenzeneHCID 680234-FluorobenzaldehydeHCID 178418339Butyllithium2×

Product 1

HCID 199623883-Bromo-5-[(4-fluorophenyl)hydroxymethyl]benzaldehydeYield 70.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

A 2.5M solution of n-butyllithium in hexane (22.0 ml) was added dropwise to a stirred suspension of 1,3,5-tribromobenzene (15.74 g) in dry diethyl ether (500 ml) at -78° C. under an atmosphere of dry nitrogen. The resulting mixture was stirred at this temperature for 30 minutes and then 4-fluorobenzaldehyde (6.83 g) was added dropwise. Stirring at -78° C. was continued for a further 30 minutes and then another equivalent of n-butyllithium (22.0 ml of 2.5M solution in hexane) was added dropwise. The mixture was stirred at -78° C. for another 15 minutes and then N,N-dimethylformamide (15.45 g) was added. Stirring was continued for 1 hour and then water (200 ml) was added. The mixture was allowed to reach room temperature and the organic layer was separated and dried (MgSO4). Evaporation of the solvent gave an oil which was chromatographed on silica gel. Elution with dichloromethane gave impurity, and further elution with dichloromethane/methanol (99:1) gave the title compound as a gum (10.94 g), Rf 0.2 (SS 3). Found: C,53.99; H,3.41. C14H10BrFO2 requires C,54.39; H,3.26%

Workup

  1. stirringStirring at -78° C.
  2. waitwas continued for a further 30 minutes
  3. stirringThe mixture was stirred at -78° C. for another 15 minutes
  4. stirringStirring
  5. waitwas continued for 1 hour
  6. customto reach room temperature
  7. customthe organic layer was separated
  8. dry with materialdried (MgSO4)
  9. customEvaporation of the solvent
  10. customgave an oil which
  11. customwas chromatographed on silica gel
  12. washElution with dichloromethane
  13. customgave
  14. washimpurity, and further elution with dichloromethane/methanol (99:1)

Sources & evidence

ORD record
ord-ff27c15ac276492a869dd3f5e12a61ea
Source dataset
uspto-grants-1997_04
Patent number
US05618941

Linked notes

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