Nitrogen → HCID 86690098, compound

To a solution of ethyl 4-oxocyclohexanecarboxylate (0.47 mL, 2.94 mmol) and dibromodifluoromethane (0.54 mL, 5.88 mmol) in N,N-dimethylacetamide (3.5 mL) was added triphenylphosphine (1.54 g, 5.88 mmol) in N,N-dimethylacetamide (3.5 mL) dropwise under N2 at 0° C. over 15 min. The reaction mixture was stirred at ambient temperature for 1 h, then zinc (0.384 g, 5.88 mmol) was added over 1 min. The mixture was stirred at rt for 20 min and then heated at 70° C. for 16 hr. The reaction was diluted with DCM, filtered through diatomaceous earth (Celite®) and the filtrate was washed with sat. NaHCO3, water and sat. NaCl, dried over anhydrous Na2SO4, filtered and concentrated to an oil. The crude product was charged to a 40 g silica gel cartridge which was eluted with a 20 min gradient of 0-20% EtOAc in hexane to yield ethyl 4-(difluoromethylene)cyclohexanecarboxylate (0.015 g). 1H NMR (400 MHz, CDCl3) ppm 4.10-4.20 (2H, m), 2.35-2.52 (3H, m), 1.95-2.05 (2H, m), 1.79-1.93 (2H, m), 1.48-1.63 (3H, m), 1.25-1.31 (3H, m).

1. stirringThe mixture was stirred at rt for 20 min
2. temperatureheated at 70° C. for 16 hr
3. filtrationfiltered through diatomaceous earth (Celite®)
4. washthe filtrate was washed with sat. NaHCO3, water and sat. NaCl
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated to an oil
8. additionThe crude product was charged to a 40 g silica gel cartridge which
9. washwas eluted with a 20 min gradient of 0-20% EtOAc in hexane

ORD record

ord-db45dd54f2bf43e7a876df1c38efe0f8

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09326973B2