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2,4-Difluoro-6-aminophenol Hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; H2; nitrogen;palladium; In methanol;
2,4-Difluoro-6-aminophenol Hydrochloride (715) A mixture of 2,4-Difluoro-6-nitrophenol (28.4 g, 0.162 mol; prepared by a similar method as 711 except replacing 2-chloro-4-fluorophenol with 2,4-difluorophenol) and 10% palladium on carbon (3.5 g) in absolute MeOH (120 mL) was placed under 1 atm of H2 and stirred until complete reduction had occurred. The H2 was replaced with nitrogen and the reaction was filtered through Celite. Gaseous HCl was bubbled through the filtrate and the resulting solution concentrated. The residue was taken up into H2 O, washed with Et2 O (2*), neutralized with solid NaHCO3 and the product extracted with Et2 O. The extracts were combined dried over MgSO4 and filtered. The filtrate was treated with gaseous HCl and resulting precipitate collected and dried under vacuum to provide 12.9 g of compound 715 as a beige solid. STR94
With nitric acid; acetic acid; at 10.0℃; for 1.5h;
Step 1: To a solution of 2A (100.0 g, 0.769 mol) in AcOH (800 mL) was added dropwise HNO3/AcOH (200 mL, v/v=1/1). The mixture was stirred at 10 C. for 90 min and then poured into ice-water (4 L). The solid was collected by filtration and washed by small amount of water to afford 2B (125 g, 93%), which was used in the next step without further purification.
With nitric acid; In acetic acid;
C.1 2,4-Difluoro-6-nitrophenol To a mixture of nitric acid (100 ml) and acetic acid (100 ml) was added a solution of 2,4-difluorophenol (13 g, 100 mmoles) in acetic acid (100 ml) dropwise at -5 under stirring. Stirring continued for 2 hours. The reaction mixture was poured into ice. The precipitate was collected, washed with water and dried to leave 11.26 g of a yellow solid. The material was used in the next step without further purification. 1H NMR: 11.15 (br.s., 1H), 7.68-7.79 (m, 2H).
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120.0℃; for 2.0h;
To a solution of 2B (125.0 g, 0.714 mol) in DMF (800 mL) at 25 C. was added 2-bromoethanol (220.0 g, 1.785 mol) and DIPEA (454.0 g, 3.570 mol). The mixture was stirred at 120 C. for 2 h. The reaction solution was diluted with water (8 L), extracted by EtOAc (4 L), dried over Na2SO4. The crude product was purified by column chromatography to afford 2C (116 g, 73%) as a yellow oil.