Hydrochloric Acid → N-(2-methylsulfinyl-1,1-dimethyl-ethyl)-N'-(2-methyl-4-(1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl)phenyl)phthalamide

Temperature

20 °C

A mixture of 2-methyl-1-methylthio-2-propanamine (11.61 g) and triethylamine (1.97 g) was added dropwise to a mixture of phthalic anhydride (14.42 g) and 1,2-dichloroethane (58 mL) at 50° C. The resulting mixture was stirred at the same temperature for 30 minutes to prepare N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acid. Aqueous sodium hydrogencarbonate solution (9.81 g/101 mL) was added dropwise to this mixture at 40° C. and then methyl chloroformate (11.04 g) was added dropwise thereto at the same temperature. After completion of the dropwise addition, the reaction mixture was stirred at 50° C. for 1 hour and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. This solution was added dropwise to a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]aniline (25.45 g), concentrated hydrochloric acid (0.49 g) and 1,2-dichloroethane (14.4 mL) at 60° C., and then stirred at 65° C. for 30 minutes to prepare a solution of N2-[1,1-dimethyl-2-(methylthio)ethyl]-N1-{2-methyl-4-{1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl}phenyl}-1,2-benzenedicarboxamide in 1,2-dichloroethane. Formic acid (0.94 g) was added to this solution, followed by adding dropwise thereto 35% hydrogen peroxide (10.41 g) at 60° C. After completion of the dropwise addition, the resulting mixture was stirred at 60° C. for 1 hour and an aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. Then, the resulting mixture was neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 43.89 g (yield 83%) of the title compound.

1. additionAfter completion of the dropwise addition
2. stirringthe reaction mixture was stirred at 50° C. for 1 hour
3. customthe organic layer was separated
4. customto prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane
5. stirringstirred at 65° C. for 30 minutes
6. additionby adding dropwise
7. customat 60° C
8. additionAfter completion of the dropwise addition
9. stirringthe resulting mixture was stirred at 60° C. for 1 hour
10. customafter which the organic layer was separated
11. customThe organic layer obtained
12. customThe crystals precipitated
13. filtrationwere filtered
14. washwashed with water
15. customdried

ORD record

ord-dd8bf3b2ba8c4f45a3a67dbd6e205b8e

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07763750B2