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

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.

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)

ORD record

ord-57468cd15ff744c6a21515147ecea2f5

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09120774B2