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

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.

1. concentrationthe resulting mixture was concentrated under reduced pressure
2. dissolutionThe resulting solid was dissolved in 50 mL of benzene
3. stirringthe reaction mixture was stirred for 30 min
4. customthe solvent was removed under reduced pressure
5. dissolutionThe resulting methyl ester was dissolved in 12 mL of CH2Cl2
6. stirringthe mixture was stirred for 15 min
7. stirringthe resulting mixture was stirred at rt overnight
8. stirringThe mixture was stirred vigorously for 1 h
9. filtrationfiltered
10. dissolutionThe filtered solids were dissolved with CH2Cl2
11. washwashed with brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated under reduced pressure
14. customto give one pure crop
15. customThe filtrate was separated
16. washwashed with brine
17. dry with materialdried over Na2SO4
18. concentrationconcentrated under reduced pressure
19. customThe residue was triturated with hot ethanol
20. customto give a second pure crop

ORD record

ord-6e57340edd55485ebed4f0adcdd6737f

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06809199B2