Dimethylformamide → 1-Methoxy-3,5-bis(methoxymethoxy)benzene

HRID 2272776Notes

Reaction equation

HRID 2272776 reaction equation
[CH:1](N(CC)C(C)C)(C)C.[CH3:10][O:11][C:12]1[CH:13]=[C:14]([OH:19])[CH:15]=[C:16]([OH:18])[CH:17]=1.[CH3:20][O:21][CH2:22]Cl.CN(C)[CH:26]=[O:27]>>[CH3:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH2:20][O:21][CH3:22])[CH:15]=[C:14]([O:19][CH2:1][O:27][CH3:26])[CH:13]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 7864Chloromethyl Methyl EtherHCID 71648FlamenolHCID 81531Diisopropylethylamine

Product 1

HCID 251409981-Methoxy-3,5-bis(methoxymethoxy)benzeneYield 43%

Conditions

Temperature
0 °C

Procedure

N,N-diisopropylethylamine (3.15 mL, 18.1 mmol) was added to 5-methoxybenzene-1,3-diol (634 mg, 4.52 mmol) in anhydrous N,N-dimethylformamide (12.6 mL) over five minutes at room temperature. After 30 minutes, the solution was cooled to 0° C., methoxy methylchloride (3.02 mL, 18.1 mmol) was added, and the solution was warmed to room temperature over 12 hours. The reaction was quenched by the addition of saturated aqueous NaHCO3 at 0° C. and extracted with EtOAc (3×10 mL). Combined organic fractions were washed with saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 6:1→4:1 Hexane:EtOAc) to afford 8 as a yellow amorphous solid (441 mg, 43%): 1H NMR (CDCl3, 500 MHz) δ 6.29 (t, J=2.2 Hz, 1H), 6.21 (d, J=2.2 Hz, 2H), 5.07 (s, 4H), 3.69 (s, 3H), 3.40 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 161.394, 159.0 (2C), 97.2, 96.2 (2C), 94.5 (2C), 56.1, 55.4 (2C); IR (film) νmax 2997, 2955, 2903, 2827, 1601, 1475, 1400, 1215, 1194, 1146, 1032, 991, 924, 829, 685 cm−1; HRMS (ESI+) m/z: [M+Na]+ calcd for C11H16O5, 251.0895. found, 251.0910.

Workup

  1. temperaturethe solution was warmed to room temperature over 12 hours
  2. customThe reaction was quenched by the addition of saturated aqueous NaHCO3 at 0° C.
  3. extractionextracted with EtOAc (3×10 mL)
  4. washCombined organic fractions were washed with saturated aqueous NaCl
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography (SiO2, 6:1→4:1 Hexane:EtOAc)

Sources & evidence

ORD record
ord-03464bc72bad4578aec0699b7c319793
Source dataset
uspto-grants-2015_09
Patent number
US09120774B2

Reaction notes

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