Triphenylphosphine → 3-Bromo-5-((tetrahydro-2H-pyran-4-yl)oxy)pyridine

To a mixture of 5-bromo-3-pyridinol (5.22 g, 30 mmol), toluene (150 mL), triphenylphosphine (11.8 g, 45 mmol) and tetrahydropyran-4-ol (4.7 g, 45 mmol) was slowly added diethyl azodicarboxylate (7.1 mL, 45 mmol). The mixture was heated at reflux for 20 h, then cooled to room temperature, washed with water (3×100 mL) and then brine (100 mL), then dried (MgSO4), filtered and concentrated by rotary evaporation. The crude oil was treated with diisopropyloxide (50 mL) and the solid thus obtained was filtered and washed with diisopropyloxide (20 mL). The combined filtrates were concentrated by rotary evaporation and purified by column chromatography on silica gel, eluting with ethyl acetate/cyclohexane (20/80, v/v). Selected fractions containing the product were concentrated via rotary evaporation to give 5 g (65%) of a yellow oil.

1. temperatureThe mixture was heated
2. temperatureat reflux for 20 h
3. washwashed with water (3×100 mL)
4. dry with materialbrine (100 mL), then dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated by rotary evaporation
7. additionThe crude oil was treated with diisopropyloxide (50 mL)
8. customthe solid thus obtained
9. filtrationwas filtered
10. washwashed with diisopropyloxide (20 mL)
11. concentrationThe combined filtrates were concentrated by rotary evaporation
12. custompurified by column chromatography on silica gel
13. washeluting with ethyl acetate/cyclohexane (20/80
14. additionSelected fractions containing the product
15. concentrationwere concentrated via rotary evaporation

ORD record

ord-c371e43541764e5a9c2b37e464fa9153

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07101896B2