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 evapoated 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) δ 7.55 (t, 1 H, J=7.7 Hz), 6.94 (d, 1 H, J=8.5 Hz), 6.71 (d, 1 H, J=8.0 Hz), 5.55 (s, 2 H), 3.77 (q, 2 H, J=7.1 Hz), 1.25 (t, 3 H, J=7.1 Hz). 13C NMR (75 MHz, CDCl3) δ 162.4, 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 residue was purified by radial PLC (5% ethyl acetate/hexanes)

ORD-Eintrag

ord-0309bbf1ec4144eb99cfe296bdae0bd5

Quelldatensatz

uspto-grants-1995_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05395939