Methyl iodide → 1-Iodo-4-(2-methoxyethyl)benzene

Temperature

60 °C

Sodium hydride (60% dispersion in mineral oil, 612 mg, 15.3 mmol) was slowly added to a solution of 4-iodophenethyl alcohol (2.53 g, 10.2 mmol) in THF (12 mL) at room temperature and with stirring. At the end of the addition, the solution had become cloudy. The reaction mixture was heated to 60° C. for 2 h and then cooled to 0° C. Iodomethane (952 μL, 15.3 mmol) was slowly added to the solution and the reaction mixture was stirred overnight. Upon the completion of the reaction, the mixture was cooled to 0° C., neutralized with aq. sat. NH4Cl (25 mL) and extracted with EtOAc (3×25 mL). The combined extracts were sequentially washed with aq. sat. NH4Cl (3×20 mL), brine (20 mL) and dried (Na2SO4). The crude product was concentrated and dried over high vacuum. Chromatography of the residue (EtOAc/hexanes=1/5) gave 2.39 g (9.12 mmol) of the title product. Yield: 89%, pale yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.61 (d, J=8.2 Hz, 2H), 6.98 (d, J=8.2 Hz, 2H), 3.57 (t, J=6.8 Hz, 2H), 3.34 (s, 3H), 2.82 (t, J=6.8 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): δ 138.9, 137.5, 131.1, 91.6, 73.3, 58.9, 35.9 ppm.

1. additionAt the end of the addition
2. temperaturecooled to 0° C
3. stirringthe reaction mixture was stirred overnight
4. customUpon the completion of the reaction
5. temperaturethe mixture was cooled to 0° C.
6. extractionextracted with EtOAc (3×25 mL)
7. washThe combined extracts were sequentially washed with aq. sat. NH4Cl (3×20 mL), brine (20 mL)
8. dry with materialdried (Na2SO4)
9. concentrationThe crude product was concentrated
10. customdried over high vacuum

ORD record

ord-5c0663df192d491583a54987914beed8

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434699B2