Chloromethyl ethyl ether → 2-Chloro-6-(ethoxymethoxy)pyridine

To a solution of 13.4 g (0.1 mol) of 6-chloro-2-pyridinol in 200 mL methylene chloride at -23° C. was added 3 g sodium hydride (80%, 0.1 mol) slowly, and stirring was continued for 5 min. 10 mL of Chloromethyl ethyl ether (0.11 mol) was added dropwise at -23° C. After stirring for 15 min. at -23° C., and an additional 1 hr at room temperature, the reaction was quenched with 50 mL of water. The mixture was extracted with two 50 mL portions of methylene chloride, and the combined organic layers were washed with water and brine. After drying over sodium carbonate, the solvents were evaporated under reduced pressure. The residue was purified by radial PLC (5% ethyl acetate/hexanes) to give 7.78 g (42%) of product as a colorless oil (bp 72° C., 0.25 mmHg) and 2.14 g of recovered starting material. 1H NMR (300 MHz, CDCl3) δ7.55 (t, 1H, J=7.7 Hz), 6.94 (d, 1H, J=8.5 Hz), 6.71 (d, 1H, J=8.0 Hz), 5.55 (s, 2H), 3.77 (q, 2H, J=7.1 Hz), 1.25 (t, 3H, J=7.1 Hz). 13C NMR (75 MHz, CDCl3) δ162.4, 148.5, 141.0, 117.2, 109.3, 91.4, 65.7, 15.2. Analysis Calculated for C8H10ClNO2 : C, 51.21; H, 5.37; N, 7.47. Found: C, 51.33; H, 5.35; N, 7.46.

1. stirringAfter stirring for 15 min. at -23° C.
2. customan additional 1 hr at room temperature, the reaction was quenched with 50 mL of water
3. extractionThe mixture was extracted with two 50 mL portions of methylene chloride
4. washthe combined organic layers were washed with water and brine
5. dry with materialAfter drying over sodium carbonate
6. customthe solvents were evaporated under reduced pressure
7. customThe residue was purified by radial PLC (5% ethyl acetate/hexanes)

ORD record

ord-9da4c022efb4452383163455ae96cb19

Source dataset

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05486615