Chloromethyl Methyl Ether → 2-Methoxy-5-(methoxymethoxy)pyridine

Temperature

2.5 °C

To a solution of 6-methoxypyridin-3-ol (20 g, 0.16 mol) in DMF (200 mL) was added NaH (60% in mineral oil; 9.6 g, 0.24 mol) at 0-5° C. portion-wise. Upon the completion of addition, the mixture was continued to stir at 0-5° C. for 15 min followed by additional of chloromethyl methyl ether. The mixture was stirred at 0-5° C. for another 20 min and quenched with aqueous NH4Cl(sat). The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organic layer was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified on silica gel with 25% EtOAc/hexanes as eluent to give 2-methoxy-5-(methoxymethoxy)pyridine (24.1 g, 89.3%) as a colorless oil. 1H NMR (400 MHz; CDCl3) 7.97 (d, 1H), 7.35 (dd, 1H), 6.70 (d, 1H), 5.12 (s, 2H), 3.91 (s, 3H), 3.51 (s, 3H); MS (ESI) m/z 170.1 [M+H]+.

1. additionUpon the completion of addition
2. stirringThe mixture was stirred at 0-5° C. for another 20 min
3. customquenched with aqueous NH4Cl(sat)
4. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
5. washthe combined organic layer was washed with water and brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified on silica gel with 25% EtOAc/hexanes as eluent

ORD record

ord-f752c511eb464ce79eddde3f3d8273e4

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422279B2