HCID 86699571, compound → HCID 178506106, compound

To a solution of 5-chloro-4-iodo-2-nitroaniline (6 g, 20.1 mmol) in dioxane (100 ml) and water (10 ml) which was purged and maintained with an inert atmosphere of nitrogen was added[2,4-bis(trifluoromethyl)phenyl]boronic acid (10.3 g, 40.01 mmol), K3PO4 (8.6 g, 40.70 mmol) and Pd(pph3)4 (2.3 g, 2.04 mmol) at room temperature. The resulting solution was stirred overnight at 95° C. in an oil bath. The resulting mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column, eluting with 2% to 3% ethyl acetate in petroleum ether to produce 4-[2,4-bis(trifluoromethyl)phenyl]-5-chloro-2-nitroaniline as a crude light yellow solid (2.2 g, crude). Next, to a solution of 4-[2,4-bis(trifluoro-methyl)phenyl]-5-chloro-2-nitroaniline (2.2 g, crude) in ethanol (50 ml) was added hydrogen chloride (conc, 1.5 ml) and Zn powder (2.2 g, 33.85 mmol). The resulting solution was stirred for 2 h at 90° C. in an oil bath. The reaction was then quenched by the addition of water (300 ml), adjusted pH to 8 with aqueous sodium carbonate and then extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with brine (200 ml), dried and concentrated under vacuum to produce 4-[2,4-bis(trifluoromethyl) phenyl]-5-chlorobenzene-1,2-diamine as a crude brown solid (1.75 g, crude). Finally, a Solution of 4-[2,4-bis(trifluoromethyl)phenyl]-5-chlorobenzene-1,2-diamine (300 mg, crude) in trifluoroacetic acid (10 ml) and hydrogen chloride (conc, 2 ml) was stirred overnight at 80° C. in an oil bath. The solution was evaporated and dissolved in water (30 ml), adjusted to pH 8 with aqueous sodium carbonate 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 a silica gel column with 10% ethyl acetate in petroleum ether to produce 6-[2,4-bis(trifluoromethyl)phenyl]-5-chloro-2-(trifluoromethyl)-1H-1,3-benzodiazole as a off-white solid (132.4 mg).

1. customThe solution was evaporated
2. dissolutiondissolved in water (30 ml)
3. extractionextracted with ethyl acetate (3×50 ml)
4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
5. concentrationconcentrated under vacuum
6. customto give a residue, which
7. customwas purified by a silica gel column with 10% ethyl acetate in petroleum ether

ORD record

ord-472cbffd072b4d88b3b5dca90c2e66be

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000187B2