Potassium Carbonate → HCID 86699558, compound

Temperature

90 °C

To a solution of 4,5-dichloro-2-nitroaniline (5 g, 24.15 mmol) in DMSO (15 ml) was added potassium carbonate (6.62 g, 47.90 mmol) and 4-(trifluoromethyl)phenol (6.6 g, 40.71 mmol) in several batches. The resulting solution was stirred for 8 h at 90° C. in an oil bath maintained with an inert atmosphere of nitrogen. The reaction mixture was then quenched by the addition of water (200 ml), extracted with ethyl acetate (5×100 ml) and the organic layers combined. The resulting mixture was washed with sodium chloride (3×100 m), dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 2% to 10% ethyl acetate in petroleum ether to produce 4-chloro-2-nitro-5-[4-(trifluoromethyl)phenoxy]aniline as a yellow solid (1.43 g, 18%). Next, to a solution of 4-chloro-2-nitro-5-[4-(trifluoromethyl)phenoxy]aniline (499 mg, 1.50 mmol) in ethanol (30 ml) was added hydrogen chloride (conc) (0.4 mL) and Zn powder (586 mg) in several bacthes. The resulting solution was stirred for 1.5 h at 85° C. in an oil bath and then concentrated under vacuum. The residue was dissolved in ethyl acetate (150 ml), washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column with 2% to 10% ethyl acetate in petroleum ether to afford 4-chloro-5-[4-(trifluoromethyl)phenoxy]benzene-1,2-diamine as a red solid (359 mg, 79%). Finally, a solution of 4-chloro-5-[4-(trifluoromethyl)phenoxy]benzene-1,2-diamine (100 mg, 0.33 mmol) in trifluoroacetic acid (5 ml) and HCl ((conc), 1 ml) was stirred for 4.5 h at 80° C. in an oil bath. The solution was poured into water (100 ml), adjusted pH value of the solution to 8 with sodium bicarbonate (sat) and extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by Pre-TLC with 11% ethyl acetate in petroleum ether to produce 5-chloro-2-(trifluoromethyl)-6-[4-(trifluoromethyl)phenoxy]-1H-1,3-benzodiazole as a white solid (78.2 mg, 62%).

1. temperaturemaintained with an inert atmosphere of nitrogen
2. customThe reaction mixture was then quenched by the addition of water (200 ml)
3. extractionextracted with ethyl acetate (5×100 ml)
4. washThe resulting mixture was washed with sodium chloride (3×100 m)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under vacuum
7. customto give a residue, which
8. customwas purified by a silica gel column with 2% to 10% ethyl acetate in petroleum ether

ORD record

ord-f107d0de1f6347a2acf64e537599f59c

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000187B2