Hydrochloric Acid → 6-Fluoro-2,3-dihydro-4H-1-benzothiopyran-4-one

Temperatur

0 °C

3-(4-Fluorophenylthio)propanoic acid (3 g, 15 mmol) was dissloved in dichloromethane (30 mL) and cooled to 0° C. in an ice bath. Oxalyl chloride (10 mL) was added slowly, dimethyl formamide (1 drop) was added and the reaction mixture was stirred at 0° C. for 0.5 hours. At which point the reaction was concentrated under reduced pressure to a residue, then resuspended in dichloromethane and cooled to 0° C. in an ice bath, Cs2 (1 mL) was added and AlCl3 (4 g, 15 mmol) was added slowly. The reaction mixture was then allowed to warm to room temperature and stirred over night. Ice chips and water (250 mL) were added and stirred. Concentrated hydrogen chloride was added until pH of 2, and extracted with dichloromethane (3×150 mL). Organics were combined, washed with brine (1×100 mL) and water (1×100 mL), dried (sodium sulfate), and concentrated to a yellow solid. The solid was purified by flash column chromatography on 100 g silica gel, eluting 10% ethyl acetate in hexanes to give 6-fluoro-2,3-dihydro-4H-1-benzothiopyran-4-one (2.55 g, 93%). 1H NMR (CDCl3, 300 MHz): δ7.80-7.76 (m, 1H), 7.27-7.23 (m, 2H), 7.15-7.09 (m, 1H), 3.23 (t, 2H, J=6.4 Hz), 2.97 (t, 2H, J=6.4 Hz) ppm.

1. concentrationwas concentrated under reduced pressure to a residue
2. temperaturecooled to 0° C. in an ice bath, Cs2 (1 mL)
3. additionwas added
4. temperatureto warm to room temperature
5. stirringstirred over night
6. stirringstirred
7. extractionextracted with dichloromethane (3×150 mL)
8. washwashed with brine (1×100 mL) and water (1×100 mL)
9. dry with materialdried (sodium sulfate)
10. concentrationconcentrated to a yellow solid
11. customThe solid was purified by flash column chromatography on 100 g silica gel
12. washeluting 10% ethyl acetate in hexanes

ORD-Eintrag

ord-1c4aff40a11743fcab1fbc2d35aa98fc

Quelldatensatz

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

USRE039679E1