Dimethylformamide → 4-Methoxy-2,6-dimethylbenzaldehyde

HRID 1418765Notes

Reaction equation

HRID 1418765 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[CH3:11].C([Li])(C)(C)C.CN([CH:20]=[O:21])C>O1CCCC1.CCOCC>[CH3:11][C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[C:7]([CH3:8])[C:2]=1[CH:20]=[O:21]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 2359922-Bromo-5-methoxy-1,3-dimethylbenzeneHCID 178418306HCID 178418306, compound

Product 1

HCID 8167794-Methoxy-2,6-dimethylbenzaldehydeYield 62.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To 4-bromo-3,5-dimethylanisole (20 g, 93.0 mmol) in 500 mL of tetrahydrofuran at -78° C. was added 120 mL of tert-Butyllithium (1.7M in pentane). The reaction mixture was stirred for 30 minutes at -78° C. and then DMF (136.0 g, 186.0 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 300 mL of ether, washed with 300 mL of water, acidified 1N HCl , and 5×100 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate) to yield 2,6-dimethyl-4-methoxybenzaldehyde (6), (9.50 g, 57.8 mmol, 62%) as a white solid; 1HNMR (CDCl3 δ 2.61 (s, 6H), 3.83 (s, 3H), 6.6 (s, 2H), 10.5 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature
  2. washwashed with 300 mL of water
  3. dry with materialThe organic portion was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate)

Sources & evidence

ORD record
ord-33e5e0e6469049849a8f50684dab06af
Source dataset
uspto-grants-1999_03
Patent number
US05883294

Reaction notes

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