Chloromethyl Methyl Ether → 3-(Methoxymethoxy)pyridine

Pyridin-3-ol (25 g, 260 mmol) was added to a stirring mixture of NaH (11 g of a 60 wt % dispersion with mineral oil, 260 mmol) and DMF (350 mL) at 0° C. After 30 min, the reaction mixture was allowed to warm to RT, stirred for 90 min, and then chloromethoxymethane (20 mL, 260 mmol) was added. After 18 h, the reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3. The layers were separated, the organic material was washed with saturated aqueous NaHCO3, brine, dried (Na2SO4), filtered, and the filtrate was concentrated. The residue was dissolved with CH2Cl2, the solution was filtered through a plug of silica gel (sequential elution; 9:1→1:1 hexane-ethyl acetate), and the second filtrate was concentrated to give 10 g (27%) of 3-(methoxymethoxy)pyridine as a clear yellow oil.

1. waitAfter 18 h
2. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3
3. customThe layers were separated
4. washthe organic material was washed with saturated aqueous NaHCO3, brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationthe filtrate was concentrated
8. dissolutionThe residue was dissolved with CH2Cl2
9. filtrationthe solution was filtered through a plug of silica gel (sequential elution; 9:1→1:1 hexane-ethyl acetate)
10. concentrationthe second filtrate was concentrated

ORD record

ord-aa0bd7d213364f3798a7ce7226e28959

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173810B2