Acetyl chloride → 1-(1,1-Dimethylethyl)-2-(methoxymethoxy)benzene

HRID 900049Notes

Reaction equation

HRID 900049 reaction equation
[C:1](Cl)(C)=O.[CH3:5][O:6][CH2:7]OC.C(Cl)OC.[C:14]1([O-:20])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Na+].[OH-].[Na+].O1[CH2:28][CH2:27][CH2:26]C1>[Cl-].[Cl-].[Zn+2].CCOCC>[C:27]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[O:20][CH2:5][O:6][CH3:7])([CH3:26])([CH3:28])[CH3:1]

Participants

9

Reactant 6

HCID 6367Acetyl chloride2×HCID 7864Chloromethyl Methyl Ether2×HCID 8020DimethoxymethaneHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 4445035Phenolate Sodium

Product 1

HCID 107742011-(1,1-Dimethylethyl)-2-(methoxymethoxy)benzene

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolvent

Procedure

The following reaction was carried out in an efficient fume cupboard. To a solution of 2-tert-butylphenol (322 g, 2.1 moles) dissolved in 1.5 liters of degassed HPLC grade thf (tetrahydrofuran) in a flask fitted with an efficient condenser was added chunks of sodium (52 g, excess) and the reaction mix allowed to react for 3 hours then refluxed overnight to complete the reaction. A solution of MOMCl was formed in a 3 liter, 3 neck flask fitted with an efficient double surfaced condenser, pressure equalizing dropping funnel and a nitrogen inlet in a water bath at RT by the slow addition of AcCl (205 g, 2.6 moles) to dimethoxymethane (229 g, 3.0 moles) with a catalytic amount of ZnCl2 (2 g). Caution MOMCl is a known carcinogen and the reaction is exothermic!! After addition of the AcCl the reaction mixture is stirred for 30 minutes and the dropping funnel replaced with a septum. The thf solution of sodium phenolate added by cannula and the reaction mix stirred for 1 hour to complete the reaction. The reaction mix is deactivated by the addition of 500 mls of 2 M NaOH solution and stirring for a further 60 minutes to decompose excess MOMCl. Ether (500 mls) is added and the phases separated. The organic phase was washed with 3×500 mls of distilled water and dried over MgSO4, filtered and the ether removed on a Rota-Vap. The unreacted phenol was removed by passage through a basic alumina column using hexane as elutriation solvent. The recovered material (compound “5.1”) was purified by flash distillation under reduced pressure, 67-68° C. 0.4 mm Hg. Yield 287 g (74%). 1H-NMR (250 MHz, CDCl3) δ 1.420(s, 9H, C(CH3)3), 3.519(s, 3H, OMe), 5.253(s, 2H, OCH2O), 6.92-7.33(m, 4H, Ar—H).

Workup

  1. customfitted with an efficient
  2. customat RT
  3. additionthe reaction mix
  4. stirringstirred for 1 hour
  5. customthe reaction
  6. additionThe reaction mix
  7. stirringstirring for a further 60 minutes
  8. customthe phases separated
  9. washThe organic phase was washed with 3×500 mls of distilled water
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customthe ether removed on a Rota-Vap
  13. customThe unreacted phenol was removed by passage through a basic alumina column
  14. distillationThe recovered material (compound “5.1”) was purified by flash distillation under reduced pressure, 67-68° C

Sources & evidence

ORD record
ord-45455b4ea1ba49a886331f41a1d366df
Source dataset
uspto-grants-2008_04
Patent number
US07358209B2

Reaction notes

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