Hydrochloric Acid → (4'-Chloro-3'-fluoro-4-methylbiphenyl-3-yl)acetic acid

Under argon, 33.5 g (192 mmol) (4-chloro-3-fluorophenyl)boronic acid were added to a solution of 40.0 g (175 mmol) of (5-bromo-2-methylphenyl)acetic acid (EP 1791816 and WO 2006/29799) in a mixture of 437 ml (437 mmol) of degassed 1N aqueous sodium hydroxide solution, 160 ml of degassed water and 160 ml of degassed tetrahydrofuran. The mixture was stirred for 10 minutes, 507 mg (1.75 mmol) of tri-tert-butylphosphonium tetrafluoroborate and 532 mg (1.75 mmol) of palladium(II) acetylacetonate were added and the mixture was stirred at room temperature for 20 h. Toluene and water were then added, the pH was adjusted to 1-2 using concentrated aqueous hydrogen chloride solution, the mixture was stirred for 10 minutes, the phases were separated, the aqueous phase was extracted twice with toluene and the combined organic phases were dried over sodium sulphate, filtered and concentrated. The residue was stirred in 300 ml of a 6/1 mixture of n-hexane/tert-butyl methyl ether for 30 minutes, filtered off with suction, washed with n-hexane and dried under reduced pressure. This gave 38.0 g (78% of theory) of the title compound.

1. stirringthe mixture was stirred at room temperature for 20 h
2. stirringthe mixture was stirred for 10 minutes
3. customthe phases were separated
4. extractionthe aqueous phase was extracted twice with toluene
5. dry with materialthe combined organic phases were dried over sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated
8. stirringThe residue was stirred in 300 ml of a 6/1 mixture of n-hexane/tert-butyl methyl ether for 30 minutes
9. filtrationfiltered off with suction
10. washwashed with n-hexane
11. customdried under reduced pressure

ORD record

ord-d2c75b868e1e448d9b657370514d3115

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212140B2