Methyl 2-(4-fluorophenyl)acetate → 2-(4-Fluorophenyl)-1-[2-methyl-(4-pyridyl)]ethanone

Temperature

95 °C

To a freshly prepared solution of NaOMe (3.0 M in MeOH) was added a solution of methyl 2-methylisonicotinate (6.81 g, 45.1 mmol) in MeOH (10 mL). This was followed by the dropwise addition of a solution of methyl 4-fluorophenylacetate (8.34 g, 49.6 mmol) in MeOH (10 mL,). The MeOH was distilled off while heating the reaction mixture at 95° C. After 17.5 h, the solid residue was cooled. Concentrated HCl (15 mL) was added, and the mixture was heated at reflux. After 4 h, the mixture was cooled then diluted with H2O. The aqueous mixture was washed with Et2 O, adjusted to pH 5 with 1N NaOH, then adjusted to pH 8 with saturated NaHCO3. The alkaline aqueous was extracted with EtOAc. The EtOAc extracts were washed with saturated NaCl, then dried over Na2 SO4. Evaporation of solvent in vacuo afforded a red oil which was purified by column chromatography, eluting with a gradient of 0-3% MeOH/CHCl3. The title compound was isolated as a red oil (1.5 g, 15%).

1. distillationThe MeOH was distilled off
2. temperaturethe solid residue was cooled
3. additionConcentrated HCl (15 mL) was added
4. temperaturethe mixture was heated
5. temperatureat reflux
6. waitAfter 4 h
7. temperaturethe mixture was cooled
8. additionthen diluted with H2O
9. washThe aqueous mixture was washed with Et2 O
10. extractionThe alkaline aqueous was extracted with EtOAc
11. washThe EtOAc extracts were washed with saturated NaCl
12. customdried over Na2 SO4
13. customEvaporation of solvent in vacuo
14. customafforded a red oil which
15. customwas purified by column chromatography
16. washeluting with a gradient of 0-3% MeOH/CHCl3

ORD record

ord-ef20098771d343c7b0fb8dda939d7460

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05686455