反应详情

A mixture of 2.0 g (7.02 mmol) of 3-bromo-5-(trifluoromethoxy)benzoic acid, 906 mg (7.72 mmol) of zinc cyanide and 486 mg (0.42 mmol) of tetrakis(triphenylphosphine)palladium(0) in 23 ml of DMF was initially degassed and then, under an atmosphere of argon, heated under reflux for 4 h. A further 243 mg (0.21 mmol) of tetrakis(triphenylphosphine)palladium(0) and 453 mg (3.86 mmol) of zinc cyanide were then added, and the mixture was stirred under reflux for another 16 h. The reaction was then concentrated to a volume of about 5 ml under reduced pressure and stirred into 100 ml of 0.1 M aqueous sodium hydroxide solution. The solid formed was filtered off, the filtrate was adjusted to pH 1 with concentrated hydrochloric acid and the precipitate formed was filtered off again. The filtrate was extracted twice with in each case 50 ml of tert-butyl methyl ether, and the combined organic phases were washed with water and saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The product was isolated by preparative HPLC (Method 20). Evaporation of the product fractions and drying of the residue under high vacuum gave 75 mg (92% pure, 4% of theory) of the title compound.

1. customwas initially degassed
2. temperatureunder an atmosphere of argon, heated
3. temperatureunder reflux for 4 h
4. temperatureunder reflux for another 16 h
5. concentrationThe reaction was then concentrated to a volume of about 5 ml under reduced pressure
6. stirringstirred into 100 ml of 0.1 M aqueous sodium hydroxide solution
7. customThe solid formed
8. filtrationwas filtered off
9. customthe precipitate formed
10. filtrationwas filtered off again
11. extractionThe filtrate was extracted twice with in each case 50 ml of tert-butyl methyl ether
12. washthe combined organic phases were washed with water and saturated sodium chloride solution
13. dry with materialdried over sodium sulphate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe product was isolated by preparative HPLC (Method 20)
17. customEvaporation of the product fractions
18. customdrying of the residue under high vacuum