Ethylene Glycol → 2-(2-Hydroxyethoxy)pyridine

Ethylene glycol (30.1 g, 484 mmol), 2-chloropyridine (10.0 g, 88 mmol), powdered potassium hydroxide (9.9 g, 176.13 mmol), and 18-crown-6 ether (9.3 g, 35 mmol) were dissolved in anhydrous toluene (500 mL) under a N2 atmosphere. The reaction mixture was stirred vigorously and heated to reflux. After 48 h, the reaction reached 50% conversion. The reaction mixture was concentrated in vacuo to approximately 100 mL volume then diluted with water (100 mL). After stirring for 0.5 h, the organic layer was separated and the aqueous layer was extracted with CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was purified by Jones column chromatography (100% hexanes to 50% ethyl acetate/hexanes) to give 2-(pyridin-2-yloxy)ethanol as a dark brown oil containing 15% w/w of 18-crown-6 ether. 1H NMR (d6-DMSO, 400 MHz): δ 8.14 (ddd, J=5.0, 2.0, 1.2 Hz, 1H), 7.68 (ddd, J=9.4, 7.2, 2.4 Hz, 1H), 6.95 (ddd, J=8.0, 4.8, 1.2 Hz, 1H), 6.80 (ddd, J=8.4, 1.0, 1.0 Hz, 1H), 4.83 (t, J=5.6 Hz, 1H), 4.26 (t, J=5.2 Hz, 2H), 3.70 (dt, J=10.4, 5.2 Hz, 2H).

1. temperatureheated to reflux
2. concentrationThe reaction mixture was concentrated in vacuo to approximately 100 mL volume
3. additionthen diluted with water (100 mL)
4. stirringAfter stirring for 0.5 h
5. customthe organic layer was separated
6. extractionthe aqueous layer was extracted with CH2Cl2
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by Jones column chromatography (100% hexanes to 50% ethyl acetate/hexanes)

ORD record

ord-f575d317906444f6870a90eab1d780a9

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07521448B2