Tetrahydrothiopyran-4-one → HCID 21877813, compound

Temperature

-78 °C

To the solution of 1-(3,5-difluorophenyl)-2,5-dimethyl-1H-pyrrole (Step 1, 16.7 g, 80.6 mmol) in anhydrous THF (161 mL) at −78° C. under N2 is added n-BuLi (1.6 M in hexanes, 51.8 mL, 82.9 mmol) dropwise. After stirring at −78° C. for 1 h, the reaction mixture is treated with tetrahydrothiopyran-4-one (5.35 g, 46.1 mmol) in anhydrous THF (46 mL) dropwise and then stirred at −78° C. for 2 h and at 0° C. for 3 h. The reaction is then quenched by the slow addition of saturated aqueous ammonium chloride (50 mL), diluted with H2O (50 mL) and Et2O (50 mL) and the layers are separated. The organic phase is washed with H2O (50 mL) and saline (50 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and the residue is purified by silica gel chromatography (650 mL, 10–20% EtOAc/Hexanes eluent) to give the title compound, mp 125–126° C.; MS (ESI+) for C17H19F2NOS m/z 324 (M+H)+.

1. stirringstirred at −78° C. for 2 h and at 0° C. for 3 h
2. customThe reaction is then quenched by the slow addition of saturated aqueous ammonium chloride (50 mL)
3. additiondiluted with H2O (50 mL) and Et2O (50 mL)
4. customthe layers are separated
5. washThe organic phase is washed with H2O (50 mL) and saline (50 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customthe residue is purified by silica gel chromatography (650 mL, 10–20% EtOAc/Hexanes eluent)

ORD record

ord-97d8e9f2a11a48e88fb46d036f097f65

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07141588B2