3,3-dimethylpyridine-2,4(1H,3H)-dione → 6-(3,5-Difluorophenyl)-3,3-dimethylpiperidine-2,4-dione

To a solution of 3,3-dimethylpyridine-2,4(1H,3H)-dione (978 mg, 7.03 mmol) [U.S. Pat. No. 2,525,231] in benzene (10 mL) was added 3,5-difluorophenylmagnesium bromide (50 mL of a 0.5 M solution in THF, 25 mmol) and the resulting mixture was heated to reflux for 1.5 h. The mixture was cooled, quenched with 1 N aqueous HCl (10 mL), made basic with saturated NaHCO3 solution (100 mL) and extracted with EtOAc (2×150 mL). The combined organic layers were washed with H2O (50 mL), then brine (50 mL), and dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 60:40, to give the title compound. MS: m/z=254 (M+1).

1. temperaturewas heated
2. temperatureto reflux for 1.5 h
3. temperatureThe mixture was cooled
4. customquenched with 1 N aqueous HCl (10 mL)
5. extractionextracted with EtOAc (2×150 mL)
6. washThe combined organic layers were washed with H2O (50 mL)
7. dry with materialbrine (50 mL), and dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by silica gel chromatography
11. washeluting with a gradient of hexane

ORD record

ord-0cd066168fc34cf496291e8e888add58

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07629338B2