2,4-DICHLORO-5-FLUOROBENZYLAMINE synthesis

Yield:-

Reaction Conditions:

Stage #1: C₇H₄BrCl₂Fwith sodium hydride in tetrahydrofuran; for 0.5 h;
Stage #2: with iminodicarboxylic acid di-tert-butyl ester in tetrahydrofuran at 55;
Stage #3: with hydrogenchloride in ethyl acetate at 20; for 1.5 h;

Steps:

70

Reference example 70; To compound (1) (624mg) in THF (30ml) was added 60% sodium hydride (145mg) and the mixture was stirred for 30 minutes. And then thereto was added tert-dibutyl iminodicarboxylate (788mg) and the mixture was stirred at 55°C for 1 hour. Thereto was added additional tert-dibutyl iminodicarboxylate (788mg) and the mixture was stirred at 55°C overnight. After the reaction mixture was cooled, thereto was added ethyl acetate, and the mixture was washed with water, and dried. After removal of the solvent the residue was purified with silica gel column chromatography (hexane:ethyl acetate= 100:0→ 95:5) to give an oily product. To the product in ethyl acetate was added 4N hydrochloric acid /ethyl acetate (20ml), and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated in vacuo. The residue was crushed with diethyl ether/hexane and dried to give compound (2) (490mg) as a colorless solid. APCI-MS (m/e): 194/196 (M+H)⁺

References:

EP1956009,2008,A1 Location in patent:Page/Page column 94