Реакция #1929065

Уравнение реакции

(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

Растворители

tetrahydrofuran

water

water

Toluene

Условия реакции

Обработка

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
   Другоеthe phases were separated
4. 4
   Экстракцияthe aqueous phase was extracted twice with toluene
5. 5
   Сушкаthe combined organic phases were dried over sodium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated
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
   Фильтрацияfiltered off with suction
10. 10
    Промывкаwashed with n-hexane
11. 11
    Другоеdried under reduced pressure

Методика

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.

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