Methyl iodide → 1,3-Bis(ethoxymethoxy)-4-methoxy-2-methylbenzene

HRID 2272770Notes

Reaction equation

HRID 2272770 reaction equation
[CH2:1]([O:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][O:14][CH2:15][CH3:16])[CH:9]=[CH:8][C:7]=1[O:17][CH3:18])[CH3:2].[Li][CH2:20]CCC.CI>C1COCC1>[CH2:15]([O:14][CH2:13][O:12][C:10]1[CH:9]=[CH:8][C:7]([O:17][CH3:18])=[C:6]([O:5][CH2:4][O:3][CH2:1][CH3:2])[C:11]=1[CH3:20])[CH3:16]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 251409932,4-Bis(ethoxymethoxy)-1-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 251402551,3-Bis(ethoxymethoxy)-4-methoxy-2-methylbenzeneYield 57.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 4a (632 mg, 2.27 mmol) in anhydrous THF (1.94 mL) was added dropwise to a solution of nBuLi (2.5 M in hexanes, 1.48 mL, 3.70 mmol) in anhydrous THF (1.62 mL) at room temperature. After one hour, the solution was cooled to −78° C. and methyl iodide (620 μL, 9.87 mmol) was added. The resulting solution was warmed to room temperature over 12 hours, and the reaction was quenched by the addition of saturated aqueous NH4Cl. Water (5 mL) was added and the solution was extracted with CH2Cl2 (3×10 mL). Combined organic fractions were dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 8:1→5:1 Hexane:EtOAc) to afford 5a as a yellow oil (353 mg, 53%): 1H NMR (CDCl3, 500 MHz) δ 6.74 (d, J=9.0 Hz, 1H), 6.60 (d, J=9.0 Hz, 1H) 5.10 (s, 2H), 5.05 (s, 2H), 3.78 (q, J=7.1 Hz, 2H), 3.72 (s, 3H), 3.67 (q, J=7.1 Hz, 2H), 2.14 (s, 3H), 1.18-1.15 (m, 6H); 13C NMR (CDCl3, 125 MHz) δ 149.1, 146.5, 121.7, 109.0, 108.4, 96.2, 93.0, 64.3, 63.1, 55.1, 28.7, 14.2, 14.1, 8.8; IR (film) νmax 2918, 2359, 1487, 1260, 1248, 1082, 1055, 945, 798 cm−1; HRMS (ESI+) m/z: [M+Na]+ calcd for C14H22O5, 293.1365. found, 293.1357.

Workup

  1. temperatureThe resulting solution was warmed to room temperature over 12 hours
  2. customthe reaction was quenched by the addition of saturated aqueous NH4Cl
  3. additionWater (5 mL) was added
  4. extractionthe solution was extracted with CH2Cl2 (3×10 mL)
  5. dry with materialCombined organic fractions were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography (SiO2, 8:1→5:1 Hexane:EtOAc)

Sources & evidence

ORD record
ord-57468cd15ff744c6a21515147ecea2f5
Source dataset
uspto-grants-2015_09
Patent number
US09120774B2

Reaction notes

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