Chloromethyl Methyl Ether → 6-methoxy-2-(methoxymethoxy)benzaldehyde

HRID 1854659Notes

Reaction equation

HRID 1854659 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH3:11])[C:3]=1[CH:4]=[O:5].C(N(CC)C(C)C)(C)C.[CH3:21][O:22][CH2:23]Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.Cl>[CH3:11][O:10][C:6]1[C:3]([CH:4]=[O:5])=[C:2]([O:1][CH2:21][O:22][CH3:23])[CH:9]=[CH:8][CH:7]=1

Participants

8

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 696926-MethoxysalicylaldehydeHCID 81531Diisopropylethylamine

Product 1

HCID 111271826-methoxy-2-(methoxymethoxy)benzaldehydeYield 87.3%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Hydroxy-6-methoxybenzaldehyde (200 mg, 1.31 mmol) was placed in a 20 mL reaction vessel, and dissolved in 3.9 mL of dry dichloromethane. To the solution were added N,N-diisopropylethylamine (0.70 mL, 4.0 mmol), 4-dimethylaminopyridine (20 mg, 0.16 mmol), and chloromethyl methyl ether (250 μL, 3.28 mmol). After being stirred at room temperature overnight, the reaction mixture was diluted with 70 mL of ethyl acetate and 15 mL of 1N HCl, and extracted. The extract was washed with 1N HCl, saturated NaHCO3 aqueous solution, brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound as a pale yellow oil (224.4 mg, 87%).

Workup

  1. extractionextracted
  2. washThe extract was washed with 1N HCl, saturated NaHCO3 aqueous solution, brine
  3. dry with materialdried over MgSO4
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated in vacuo
  6. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-6f15a5fd0c8a477bbe8505de6e02fcf6
Source dataset
uspto-grants-2015_02
Patent number
US08962674B2

Reaction notes

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