2,6-Dichloroaniline → 3-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]-N-(2,6-dichlorophenyl)propanamide

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Reaction Steps

tert-butyl 3-[-4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]propanoate (3.42 g, 6.93 mmol) was dissolved in 12 mL of trifluoroacetic acid and stirred at rt for 0.75 h. 30 mL of toluene was added and the resulting mixture was concentrated under reduced pressure. The resulting solid was dissolved in 50 mL of benzene and 5 mL of methanol. A 2M solution of (trimethylsilyl)diazomethane in hexanes (4.16 mL, 8.32 mmol) was added dropwise and the reaction mixture was stirred for 30 min. 2 drops of trifluoroacetic acid were added and the solvent was removed under reduced pressure. The resulting methyl ester was dissolved in 12 mL of CH2Cl2. To 2,6-dichloroaniline (2.25 g, 13.9 mmol) in 36 mL of CH2Cl2 was added dropwise a 2M solution of trimethylaluminum in toluene (7.0 mL, 13.9 mmol) and the mixture was stirred for 15 min. Then the methyl ester solution in CH2Cl2 was added and the resulting mixture was stirred at rt overnight. 24 mL of water was added very carefully followed by 12 mL of an aqueous 1M solution of potassium sodium tartarate and 24 mL of CH2Cl2. The mixture was stirred vigorously for 1 h and then filtered. The filtered solids were dissolved with CH2Cl2, washed with brine, dried over Na2SO4, and concentrated under reduced pressure to give one pure crop. The filtrate was separated, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was triturated with hot ethanol to give a second pure crop. The two crops were combined to give the 3-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]-N-(2,6-dichlorophenyl)propanamide as a white solid.

Provenance & Evidence