4-Chloroaniline → 5-bromo-N-(4-chlorophenyl)-2-methoxybenzamide

Temperature

0 °C

5-Bromo-2-methoxybenzoic acid (20 g) obtained in step B and 0.34 mL of N,N-dimethylformamide were dissolved in 380 mL of dichloromethane, and the solution was cooled to 0° C. This solution was stirred for 30 minutes at 0° C., with oxalyl chloride (11.3 mL) being added little by little thereto, and then the mixture was stirred for 3 hours at room temperature. The reaction mixture was distilled under reduced pressure and dried to obtain a light yellow solid. This solid was added, with the use of 120 mL of dichloromethane, to a solution of 11.1 g of 4-chloroaniline and 45 mL of N,N-diisopropylethylamine dissolved in 380 mL of dichloromethane. The mixture was stirred for 2 hours and a half at room temperature, and then 300 mL of water was added. The organic layer was separated, and the aqueous layer was extracted twice with 100 mL of dichloromethane. After the respective organic layers were combined, the combined organic layer was washed with 200 mL of a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was separated by filtration, and then washed with dichloromethane. The filtrate and the washings were combined, dichloromethane was distilled off under reduced pressure, and the resulting residue was washed with methanol. The resulting solid was dried under reduced pressure to obtain 23.6 g (80%) of 5-bromo-N-(4-chlorophenyl)-2-methoxybenzamide.

1. additionbeing added little by little thereto, and then the mixture
2. distillationThe reaction mixture was distilled under reduced pressure
3. customdried
4. customto obtain a light yellow solid
5. stirringThe mixture was stirred for 2 hours
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted twice with 100 mL of dichloromethane
8. washthe combined organic layer was washed with 200 mL of a saturated aqueous solution of sodium bicarbonate
9. dry with materialdried over anhydrous sodium sulfate
10. customThe anhydrous sodium sulfate was separated by filtration
11. washwashed with dichloromethane
12. distillationdichloromethane was distilled off under reduced pressure
13. washthe resulting residue was washed with methanol
14. customThe resulting solid was dried under reduced pressure

ORD record

ord-477840451b304f58914c31fdd07a697d

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063046B2