Reaktion #1929065

Reaktionsgleichung

(4-chloro-3-fluorophenyl)boronic acid

(5-bromo-2-methylphenyl)acetic acid

sodium hydroxide

tri-tert-butylphosphonium tetrafluoroborate

hydrogen chloride

→

(4′-Chloro-3′-fluoro-4-methylbiphenyl-3-yl)acetic acid

Lösungsmittel

tetrahydrofuran

water

water

Toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred at room temperature for 20 h
2. 2
   workup.STIRRINGthe mixture was stirred for 10 minutes
3. 3
   Sonstigethe phases were separated
4. 4
   Extraktionthe aqueous phase was extracted twice with toluene
5. 5
   Trocknenthe combined organic phases were dried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   workup.STIRRINGThe residue was stirred in 300 ml of a 6/1 mixture of n-hexane/tert-butyl methyl ether for 30 minutes
9. 9
   Filtrationfiltered off with suction
10. 10
    Waschenwashed with n-hexane
11. 11
    Sonstigedried under reduced pressure

Vorschrift

Under argon, 33.5 g (192 mmol) of (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 with 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 sulfate, 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.

Quelle