Chloromethyl Methyl Ether → HCID 67119201, compound

HRID 2076595Notes

Reaction equation

HRID 2076595 reaction equation
[CH:1]([O:6][CH3:7])([O:4][CH3:5])OC.[C:8]([C:12]1C(O)=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH:15]=[O:16])([CH3:11])([CH3:10])[CH3:9].[C:21](=[O:24])([O-])O.[Na+].[H-].[Na+].[CH3:28]OCCl>CO.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.O>[C:8]([C:12]1[CH:19]=[CH:18][CH:17]=[C:14]([CH:15]([O:16][CH3:28])[O:24][CH3:21])[C:7]=1[O:6][CH2:1][O:4][CH3:5])([CH3:9])([CH3:10])[CH3:11]

Participants

9

Reactant 5

HCID 7864Chloromethyl Methyl EtherHCID 9005Trimethyl orthoformateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 36786753-tert-Butyl-2-hydroxybenzaldehyde

Product 1

HCID 67119201HCID 67119201, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

After trimethyl orthoformate (106 ml, 0.972 mol) and camphorsulfonic acid (0.751 g, 3.24 mmol) were added to a solution of 3-tert-butyl-2-hydroxybenzaldehyde (28.8 g, 162 mmol) which was synthesized according to the method described in literature (Hofsløkken, N. U. et al., Acta Chem. Scand., 1999, vol. 53, pp. 258-262) in methanol (20 ml), the mixture was stirred at 50° C. for 6 hours. After the reaction mixture was poured into a 1% aqueous sodium hydrogencarbonate solution and the mixture was extracted with ethyl acetate (three times), the organic layer was successively washed with water (twice) and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by concentrating the organic layer was dissolved in N,N-dimethylformamide (100 ml). After sodium hydride (55% oily, 7.77 g, 178 mmol) was added to the solution under ice-cooling and the mixture was stirred for 30 minutes, chloromethyl methyl ether (13.5 ml, 178 mmol) was added thereto and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was poured into water and the mixture was extracted with ethyl acetate (twice), the organic layer was successively washed with 0.5N hydrochloric acid, a 5% aqueous sodium hydrogencarbonate solution, water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=14/1-10/1) to give 1-tert-butyl-3-(dimethoxymethyl)-2-(methoxymethoxy)benzene (10.4 g, yield: 24%).

Workup

  1. customwas synthesized
  2. extractionthe mixture was extracted with ethyl acetate (three times)
  3. washthe organic layer was successively washed with water (twice) and a saturated aqueous NaCl solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. customThe residue obtained
  6. concentrationby concentrating the organic layer
  7. dissolutionwas dissolved in N,N-dimethylformamide (100 ml)
  8. temperaturecooling
  9. stirringthe mixture was stirred at room temperature for 2 hours
  10. extractionthe mixture was extracted with ethyl acetate (twice), the organic layer
  11. washwas successively washed with 0.5N hydrochloric acid
  12. dry with materiala 5% aqueous sodium hydrogencarbonate solution, water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
  13. customThe residue obtained
  14. customby removing the solvent under reduced pressure
  15. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=14/1-10/1)

Sources & evidence

ORD record
ord-c869412762494df7b685fdad585beff4
Source dataset
uspto-grants-2011_04
Patent number
US07923573B2

Reaction notes

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