Hydrochloric Acid → 4-(Methoxymethoxymethyl)-2-methylbenzaldehyde

HRID 501792Notes

Reaction equation

HRID 501792 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][O:11][CH3:12])=[CH:4][C:3]=1[CH3:13].CN(C)[CH:16]=[O:17].O.Cl>O1CCCC1.C([Li])CCC.CCCCCC>[CH3:12][O:11][CH2:10][O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH:16]=[O:17])=[C:3]([CH3:13])[CH:4]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 6228DimethylformamideHCID 684578621-Bromo-4-((methoxymethoxy)methyl)-2-methylbenzene

Product 1

HCID 230215454-(Methoxymethoxymethyl)-2-methylbenzaldehyde

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 178418339ButyllithiumSolvent

Conditions

Temperature
-65 °C

Procedure

4.00 g of 1-bromo-4-[(methoxymethoxy)methyl]-2-methylbenzene was dissolved in 40 mL of tetrahydrofuran, to which 11.5 mL of a solution of n-butyllithium in n-hexane (1.56 M) was added dropwise at −65 to −60° C., and then this mixture was stirred for 30 minutes at −65° C. Then, 20 mL of N,N-dimethylformamide was added dropwise thereto at −65 to −40° C., and a temperature of this reaction mixture was raised to room temperature over one hour and was stirred for another one hour at room temperature. Water was added to the reaction mixture and adjusted to pH 5 with 6M hydrochloric acid, followed by addition thereto of ethyl acetate, and then the organic phase was separated therefrom. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous magnesium sulfate, and the solvent was distilled out under reduced pressure. The resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=5:1] to yield 1.54 g of 4-[(methoxymethoxy)methyl]-2-methylbenzaldehyde as colorless oil.

Workup

  1. additionwas added dropwise at −65 to −60° C.
  2. temperatureat −65 to −40° C., and a temperature of this reaction mixture was raised to room temperature over one hour
  3. stirringwas stirred for another one hour at room temperature
  4. additionfollowed by addition
  5. customof ethyl acetate, and then the organic phase was separated
  6. washAfter the resultant organic phase was washed with water
  7. dry with materiala saturated sodium chloride solution successively, the washed phase was dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled out under reduced pressure
  9. customThe resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=5:1]

Sources & evidence

ORD record
ord-e4c1dba4962a48189a403b9116c41837
Source dataset
uspto-grants-2010_08
Patent number
US07772285B2

Reaction notes

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