2,5-Difluoroaniline → N-(2,5-difluorophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amine

Temperature

0 °C

A mixture of 2.5-difluoroaniline (2.58 g, 20 mmol) and 3-(1,1,2,2-tetrafluoroethoxy)benzaldehyde (4.44 g, 20 mmol) in cyclohexane (50 mL) was heated under reflux for 5 h using a Dean-Stark trap to remove water. The solvent was removed in vacuo, and the residue was dissolved in methanol (30 mL). The solution was stirred and cooled to 0° C., then sodium borohydride was added (1.32 g, 35 mmol). The mixture was allowed to warm to room temperature and stirred for 2 h, then acidified with 1N HCl. After neutralizing to pH 7.5 with 2.5 N sodium hydroxide, the mixture was extracted with diethyl ether (3×20 mL). The organic layer was washed with brine and water, then dried over anhydrous MgSO4, and evaporated to give 5.7 g (86%) of the desired N-(2,5-difluorophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amine product as a brown oil, which was greater than 90% pure by reverse phase HPLC analysis. MS m/z=336 [M+].

1. temperaturewas heated
2. temperatureunder reflux for 5 h
3. customto remove water
4. customThe solvent was removed in vacuo
5. dissolutionthe residue was dissolved in methanol (30 mL)
6. additionsodium borohydride was added (1.32 g, 35 mmol)
7. temperatureto warm to room temperature
8. stirringstirred for 2 h
9. extractionthe mixture was extracted with diethyl ether (3×20 mL)
10. washThe organic layer was washed with brine and water
11. dry with materialdried over anhydrous MgSO4
12. customevaporated

ORD record

ord-b128e86e08f54021b09e0745bcc9d30f

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06458852B1