Triethylamine → Phthalimide

Participants

Reaction Steps

To a stirred solution of 2,3-difluoro-4-methylbenzyl bromide (Matrix, 10.47 g) and N-hydroxyphthalimide (7.73 g) in DMF (100 ml) was added drop-wise triethylamine (Et3N) (7.3 ml) (DBU may be used as an alternative to Et3N). The red reaction mixture was stirred at room temperature for 2 hours. On addition of 1 M HClaq. a white precipitate formed, that was isolated by filtration and washed with water and dried in vacuo affording a phthalimide intermediate (12.55 g, white shiny material). This compound (6.07 g) was dissolved in dichloromethane and methyl-hydrazine (1.16 ml) was added drop-wise. The reaction mixture was stirred at room temperature for 30 min. and the solid material was removed by filtration. The filtrate was evaporated under reduced pressure and purified by chromatography on silica gel (EtOAc/petroleum ether as eluent) and gave the title amine as a clear colourless oil (3.34 g). Alternatively the phthalimide intermediate can be treated with hydrazine monohydrate (1.0 eq.) in refluxing ethanol for 2-3 hours and the title compound obtained as the hydrochloride salt by treatment with 4M HCl in dioxane as described above for preparation 14. HCl salt: 13C-NMR (DMSO-d6) δ 150.0, 146.8, 128.4, 126.2, 126.1, 120.3, 68.9, 13.9. Free amine: 13C-NMR (CDCl3) δ149.2, 149.3, 127.0, 125.4, 124.5, 124.0, 70.9, 14.3

Provenance & Evidence