18-Crown-6 → Methyl 1-(difluoromethyl)-6-oxo-1,6-dihydropyridine-3-carboxylate

Temperature

90 °C

A mixture of methyl 6-acetamidonicotinate (1.93 g, 9.94 mmol), sodium chlorodifluoroacetate (1.818 g, 11.93 mmol, Alfa Aesar Avocado Lancaster) and 18-crown-6 (0.525 g, 1.988 mmol, Aldrich) in MeCN (40 mL) was heated to 90° C. (reflux) under nitrogen. After 5 h, a solution of KHSO4 (1% in H2O, 10 mL) was added and the mixture was refluxed for 21 h. The mixture was then cooled to room temperature and concentrated. The mixture was diluted with EtOAc (250 mL), washed with 10% aqueous hydrochloric acid (100 mL), and then with saturated aqueous NaHCO3 (100 mL), and finally with brine (100 mL). The mixture was dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (5 mL), and the solution was purified by silica gel flash column chromatography (5-30% EtOAc/hexane) to afford the title compound as a white solid. MS (ESI, positive ion) m/z: 204 (M+H).

1. temperature(reflux) under nitrogen
2. temperaturethe mixture was refluxed for 21 h
3. temperatureThe mixture was then cooled to room temperature
4. concentrationconcentrated
5. additionThe mixture was diluted with EtOAc (250 mL)
6. washwashed with 10% aqueous hydrochloric acid (100 mL)
7. dry with materialThe mixture was dried (MgSO4)
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in DCM (5 mL)
10. customthe solution was purified by silica gel flash column chromatography (5-30% EtOAc/hexane)

ORD record

ord-8fd3d85a54b6474891f5ab4fc4835e66

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096527B2