Methyl iodide → 1,3-Difluoro-5-(methoxymethyl)benzene

Temperature

2.5 °C

To a solution of (3,5-difluorophenyl)methanol (1.98 g, 13.7 mmol) in THF (20 mL) at 0° C. was added sodium hydride (1.0 g, 25 mmol) in portions. The mixture was stirred at 0-5° C. for 1 h, and then methyl iodide (4.3 mL, 69 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was quenched with water and extracted with EtOAc. The combined organic extracts were concentrated and the resulting residue was columned on 40 g silica gel, eluting with 0-40% EtOAc in hexanes, to give a colorless oil (2.1 g, 97%). 1H NMR (300 MHz, CDCl3) δ 6.86 (m, 2H), 6.71 (m, 1H), 4.43 (s, 2H), 3.38 (s, 3H) ppm.

1. stirringThe reaction mixture was stirred at room temperature for 2 h
2. customThe mixture was quenched with water
3. extractionextracted with EtOAc
4. concentrationThe combined organic extracts were concentrated
5. washeluting with 0-40% EtOAc in hexanes

ORD record

ord-17e4651a738d4e6f99c0498589833436

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200004B2