반응 #1929065

반응 방정식

(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

용매

tetrahydrofuran

water

water

Toluene

반응 조건

후처리

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
   기타the phases were separated
4. 4
   추출the aqueous phase was extracted twice with toluene
5. 5
   건조the combined organic phases were dried over sodium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated
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
   여과filtered off with suction
10. 10
    세척washed with n-hexane
11. 11
    기타dried under reduced pressure

실험 절차

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.

출처