Hydrochloric Acid → 2-(4-Fluorophenyl)thiophene

Temperature

60 °C

To a stirred solution of 2-bromothiophene (100 g, 613.3 mol) in dry THF (220 mL), at 50° C., under a nitrogen atmosphere were added Pd(OAc)2 (13.8 mg, 0.06 mmol) and 1,3-bis(diphenylphosphino)propane (25.3 mg, 0.06 mmol). After 5 minutes, 1.05 M 4-fluorophenylmagnesium bromide in THF (613 mL) was added over 6.0 hours (TOF=1750). The resulting mixture was stirred for 1 hour at 60° C., then cooled to 30° C. and slowly poured into a 2M HCl aqueous solution (600 mL) in an ice bath. DCM (300 mL) was added and the resulting mixture was separated, and washed with brine (200 mL). MgSO4 (20 g) and activated charcoal (10 g) were added and the resulting mixture was stirred. The mixture was then filtered, and the filtrate concentrated to yield the title compound as a residue, which was used without further purification.

1. temperaturecooled to 30° C.
2. customthe resulting mixture was separated
3. washwashed with brine (200 mL)
4. additionMgSO4 (20 g) and activated charcoal (10 g) were added
5. stirringthe resulting mixture was stirred
6. filtrationThe mixture was then filtered
7. concentrationthe filtrate concentrated

ORD record

ord-b256a4089bea4b29861148564973b347

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056850B2