Dimethylformamide → 2,4-Bis(ethoxymethoxy)benzaldehyde

HRID 2272765Notes

Reaction equation

HRID 2272765 reaction equation
C(N([CH2:8][CH3:9])C(C)C)(C)C.[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[CH:13]=[O:14].[CH2:20]([O:22][CH2:23]Cl)[CH3:21].CN(C)[CH:27]=[O:28]>>[CH2:20]([O:22][CH2:23][O:10][C:11]1[CH:18]=[C:17]([O:19][CH2:27][O:28][CH2:8][CH3:9])[CH:16]=[CH:15][C:12]=1[CH:13]=[O:14])[CH3:21]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 72132,4-DihydroxybenzaldehydeHCID 18523Chloromethyl ethyl etherHCID 81531Diisopropylethylamine

Product 1

HCID 146296752,4-Bis(ethoxymethoxy)benzaldehydeYield 99%

Conditions

Temperature
0 °C

Procedure

N,N-Diisopropylethylamine (25.3 mL, 145 mmol) was slowly added to 2,4-dihydroxybenzaldehyde (5.00 g, 36.2 mmol) in anhydrous N,N-dimethylformamide (100 mL) over five minutes at room temperature. After 30 minutes, the solution was cooled to 0° C. and chloromethyl ethyl ether (14.2 mL, 145 mmol) was added and the mixture warmed to room temperature over 12 hours. The reaction was quenched by the addition of saturated aqueous NH4Cl solution and extracted with EtOAc (3×50 mL). The combined organic fractions were washed with saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 5:1→1:1 Hexane:EtOAc) to give 2a as a brown amorphous solid (9.10 g, 99%): 1H NMR (CDCl3, 400 MHz) δ 10.34 (d, J=2.4 Hz, 1H), 7.81 (dd, J=8.7, 2.8 Hz, 1H), 6.89 (t, J=2.5 Hz, 1H), 6.74 (m, 1H), 5.34 (d, J=2.8, 2H), 5.28 (d, J=2.8, 2H), 3.81-3.71 (m, 4H), 1.28-1.22 (m, 6H).

Workup

  1. temperaturethe mixture warmed to room temperature over 12 hours
  2. customThe reaction was quenched by the addition of saturated aqueous NH4Cl solution
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined 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, 5:1→1:1 Hexane:EtOAc)

Sources & evidence

ORD record
ord-138ad730f2d74810a025c3875d2fb7a6
Source dataset
uspto-grants-2015_09
Patent number
US09120774B2

Reaction notes

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