Chloromethyl Methyl Ether → 3-(Methoxymethoxy)pyridine

Temperature

-15 °C

Dissolve 3-hydroxypyridine (7 g, 74 mmol) in THF (20.6 mL) and DMF (34.4 mL) and cool to −15° C. Add potassium tert-butoxide (8.3 g, 74 mmol) and stir at −15° C. for 30 min. Treat the mixture with chloromethylmethyl ether (5.81 mL, 77 mmol) dropwise over 40 min. After the addition is complete, stir the mixture at −15° C. for an additional 1 h. Remove the ice bath and allow the mixture to warm slowly to 15° C. Pour the mixture into saturated aqueous sodium chloride and stir vigorously for 10 min. Extract the resulting solution with three portions of ethyl acetate. Combine the organic extracts and wash with saturated aqueous sodium chloride, dry over sodium sulfate, filter, and concentrate in vacuo. 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J=3 Hz, 1H), 828 (d, J=5 Hz, 1H), 7.37-7.42 (m, 1H), 7.21-7.27 (m, 1H), 5.20 (s, 2H), 3.49 (s, 3H).

1. additionAfter the addition
2. customRemove the ice bath
3. temperatureto warm slowly to 15° C
4. additionPour the mixture into saturated aqueous sodium chloride
5. stirringstir vigorously for 10 min
6. extractionExtract the resulting solution with three portions of ethyl acetate
7. washwash with saturated aqueous sodium chloride
8. dry with materialdry over sodium sulfate
9. filtrationfilter
10. concentrationconcentrate in vacuo

ORD record

ord-4f81b5bff1c74792a357e9419a46d6af

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114872B2