Hydrochloric Acid → 4-Formyl-3,5-dimethylbenzoic acid

HRID 1866849

Reaction equation

HRID 1866849 reaction equation
Br[C:2]1[C:10]([CH3:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:12].C([Li])CCC.CN([CH:21]=[O:22])C.Cl>C1COCC1>[CH:21]([C:2]1[C:10]([CH3:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:12])=[O:22]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 179371424-Bromo-3,5-dimethylbenzoic acidHCID 178418339Butyllithium

Product 1

HCID 579788644-Formyl-3,5-dimethylbenzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 4-bromo-3,5-dimethylbenzoic acid (0.92 g, 4 mmol) in THF (10 mL) was cooled down to −100° C. with N2(I)-Et2O bath and added n-butyllithium (1.6 M in hexanes, 5 mL, 8 mmol) slowly. After completion of addition, the reaction mixture was warmed to −78° C. and DMF (0.74 mL, 8 mmol) was added dropwise. The resulting mixture was stirred at −78° C. for 1.5 h and allowed to warm to −20° C., followed by the addition of 2N aqueous HCl (30 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc, the combined organic phases were dried over MgSO4. The solvent was removed and the resulting residue was purified by flash column chromatography (eluent: EtOAc-hexanes-1:1) to yield 4-formyl-3,5-dimethyl-benzoic acid (10c).

Workup

  1. additionAfter completion of addition
  2. temperatureto warm to −20° C.
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialthe combined organic phases were dried over MgSO4
  6. customThe solvent was removed
  7. customthe resulting residue was purified by flash column chromatography (eluent: EtOAc-hexanes-1:1)

Sources & evidence

ORD record
ord-a44fef9a98e04f79b395aa9be1364564
Source dataset
uspto-grants-2009_12
Patent number
US07629488B2

Linked notes

Loading…