Ethyl Acetate → Pyrimidine, 5-(difluoromethoxy)-2-(methylthio)-

Temperatur

80 °C

To a stirring solution of 2-(methylthio)pyrimidin-5-ol (from step B) (71 mg, 0.50 mmol) in CH3CN (2.5 mL) and water (2.5 mL) at room temperature under argon was added K2CO3 (0.69 g, 5.0 mmol) and followed by 2-chloro-2,2-difluoro-1-phenylethanone (286 mg, 1.5 mmol). The reaction tube was sealed and heated at 80° C. for 5 hours. The reaction was cooled to room temperature. EtOAc (10 mL) was added to the reaction mixture, which was washed with brine (15 mL×3). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM (˜2 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes. 23 mg (23% for three steps) of 5-(difluoromethoxy)-2-(methylthio)pyrimidine was obtained as an off white solid. MS (ESI) 193 (M+H).

1. customThe reaction tube was sealed
2. temperatureThe reaction was cooled to room temperature
3. washwas washed with brine (15 mL×3)
4. dry with materialOrganic phase was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe crude product was dissolved in a small amount of DCM (˜2 ml)
8. washwas eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes

ORD-Eintrag

ord-849116b26b2f460082a8cf05715c5f0d

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08372837B2