Reacción #1851974

Ecuación de reacción

hydrogen chloride

Oxalyl chloride

3-[(4-fluorophenyl)sulfonyl]propanoic acid

AlCl3

→

6-fluoro-2,3-dihydro-4H-1-benzothiopyran-4-one

Rendimiento 93.3%

Disolventes

water

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónwas concentrated under reduced pressure to a residue
2. 2
   Temperaturacooled to 0° C. in an ice bath
3. 3
   workup.ADDITIONCS2 (1 mL) was added
4. 4
   Temperaturato warm to room temperature
5. 5
   workup.STIRRINGstirred over night
6. 6
   workup.STIRRINGstirred
7. 7
   Extracciónextracted with dichloromethane (3×150 mL)
8. 8
   Lavadowashed with brine (1×100 mL) and water (1×100 mL)
9. 9
   Secadodried (sodium sulfate)
10. 10
    Concentraciónconcentrated to a yellow solid
11. 11
    OtroThe solid was purified by flash column chromatography on 100 g silica gel
12. 12
    Lavadoeluting 10% ethyl acetate in hexanes

Procedimiento

3-[(4-fluorophenyl)sulfonyl]propanoic acid (3 g, 15 mmol) was dissolved 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): δ 7.80-7.76 (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.

Fuente