4-Bromophenol → 4-[2-(4-Bromophenoxy)ethyl]pyridine

Diethyl azodicarboxylate (4.44 mL, mmol, 40%) was slowly added to a solution of 2-pyridin-4-yl-ethanol (1.00 g, 8.12 mmol), triphenylphosphine (2.56 g, 9.74 mmol), and 4-bromophenol (1.40 g, 8.12 mmol) in THF (40.6 mL) at 0° C. under nitrogen. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched with water (150 mL) and extracted with ethyl acetate (200 mL). The organics were washed with 1N aqueous NaOH (100 mL) and brine (100 mL). The organics were dried (Na2SO4), filtered, and concentrated. The crude material was crystallized with ether:heptanes (1:1, ˜25 mL) and the solid was removed via filtration and washed with ether:heptanes. The combined filtrates were concentrated and further purified via flash chromatography using an Analogix SF25-40g column and ethyl acetate in heptane (0-30%) as the eluant to afford the title compound as a clear liquid (1.20 g, 46.2%). LC-MS m/z 278.4 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.11 (t, 2 H) 4.19 (t, J=6.44 Hz, 2 H) 6.77 (d, J=8.98 Hz, 2 H) 7.22-7.26 (m, 2 H) 7.38 (d, J=4.69 Hz, 2 H) 8.54-8.57 (m, 3 H)

1. customThe reaction mixture was quenched with water (150 mL)
2. extractionextracted with ethyl acetate (200 mL)
3. washThe organics were washed with 1N aqueous NaOH (100 mL) and brine (100 mL)
4. dry with materialThe organics were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude material was crystallized with ether:heptanes (1:1, ˜25 mL)
8. customthe solid was removed via filtration
9. washwashed with ether
10. concentrationThe combined filtrates were concentrated
11. customfurther purified via flash chromatography

ORD record

ord-c30dc0ccfb664b4b88b93a08b4f603c4

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846933B2