Water → Methyl 4-(pyridin-3-yloxy)benzoate

Temperature

135 °C

3-hydroxypyridine (6.17 g, 64.87 mmol) was dissolved in 100 mL of anhydrous DMF under argon atmosphere. Solid K2CO3 (8.96 g, 64.87 mmol) was added, followed by neat methyl 4-fluorobenzoate (10.0 g, 64.87 mmol). The reaction mixture was heated at 135° C. for 10 hrs. The absence of the starting material was confirmed by LC/MS. The reaction mixture was cooled down to ambient temperature and poured into ca. 500 mL of H2O. The resulting solution was extracted 3 times with ca. 150 mL of EtOAc (during the extraction small volumes of MeOH, Et2O and brine were added to facilitate the separation). Combined EtOAc layers were washed twice with sat. NaHCO3, twice with brine and dried over anhydrous Na2SO4. Solvent was removed in vacuo to give dark-red oil, which was purified by silica gel chromatography using 1:1 mixture of EtOAc/Hexane as eluent to give the title product (4.8 g, 32.3% yield) as yellow solid.

1. temperatureThe reaction mixture was cooled down to ambient temperature
2. extractionThe resulting solution was extracted 3 times with ca. 150 mL of EtOAc (during the extraction small volumes of MeOH, Et2O and brine
3. additionwere added
4. customthe separation)
5. washCombined EtOAc layers were washed twice with sat. NaHCO3, twice with brine
6. dry with materialdried over anhydrous Na2SO4
7. customSolvent was removed in vacuo
8. customto give dark-red oil, which
9. customwas purified by silica gel chromatography
10. addition1:1 mixture of EtOAc/Hexane as eluent

ORD record

ord-54cba4ac5cdd46a69dfe1706d5791f07

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372971B2