Hydrochloric Acid → 3-(Chloromethyl)-5-fluorobenzo[b]-thiophene

Temperature

-10 °C

A mixture of formol (37%; 31 g) and ZnCl2 (10 g) in ethyl acetate (90 ml) and HCl (12 N; 190 ml) was stirred at −10° C. HCl (gas) was allowed to bubble through the mixture until saturation (at −10° C.). 5-Fluoro-benzo[b]thiophene (0.35 mol) was added dropwise at <0° C. The reaction mixture was stirred overnight at room temperature. Toluene (200 ml) was added and the mixture was stirred vigorously. The organic layer was separated, washed with an aqueous NaHCO3 solution and with water, dried, filtered and the solvent was evaporated. The residue was triturated under hexane, filtered off and dried, yielding 58 g (82.6%) of 3-(chloromethyl)-5-fluorobenzo[b]-thiophene (interm 11).

1. customto bubble through the mixture until saturation (at −10° C.)
2. stirringThe reaction mixture was stirred overnight at room temperature
3. stirringthe mixture was stirred vigorously
4. customThe organic layer was separated
5. washwashed with an aqueous NaHCO3 solution and with water
6. customdried
7. filtrationfiltered
8. customthe solvent was evaporated
9. customThe residue was triturated under hexane
10. filtrationfiltered off
11. customdried

ORD record

ord-2e647644c8d84a169e1656e58c60d9bb

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06576640B1