Hydrochloric Acid → HCID 86699550, compound

Temperature

85 °C

To a solution of 5-chloro-4-iodo-2-nitroaniline (5 g, 16.75 mmol) in dioxane (200 ml) was added (4-fluorophenyl)boronic acid (4.7 g, 33.59 mmol), water (20 ml), K3PO4 (7 g, 32.98 mmol), Pd(PPh3)4 (924 mg, 0.80 mmol) with an inert atmosphere of nitrogen. The resulting solution was stirred for 8 h at 95° C. and then concentrated under reduced pressure to give a residue, which was purified by a silica gel column with 5% to 20% ethyl acetate in petroleum ether to produce 5-chloro-4-(4-fluorophenyl)-2-nitroaniline as a yellow solid (4.1 g, 91%). Next, a solution of 5-chloro-4-(4-fluorophenyl)-2-nitroaniline (4.1 g, 15.38 mmol) in ethanol (100 ml) was added to hydrogen chloride (4 ml, 48 mmol, conc) and Zn (6 g, 460 mmol) at room temperature. The resulting solution was stirred for 3 h at 85° C. The resulting mixture was concentrated under vacuum and dissolved in water (200 ml), adjusted pH to 8 with aqueous sodium bicarbonate and extracted with dichloromethane (3×200 ml). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a residue, which was purified by a silica gel column with 5% to 10% ethyl acetate in petroleum ether to produce 4-chloro-5-(4-fluorophenyl)benzene-1,2-diamine as a brown oil (2.5 g, 70%). Finally, a solution of 4-chloro-5-(4-fluorophenyl)benzene-1,2-diamine (100 mg, 0.42 mmol) in hydrogen chloride (1 ml) and trifluoroacetic acid (5 ml) was stirred overnight at 80° C. The reaction was quenched by the addition of water (50 ml) and the pH value of the solution adjusted to 7 with aqueous sodium bicarbonate. The resulting solution was extracted with ethyl acetate (3×50 ml) and the organic layers combined and dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a residue, which was purified by Pre-TLC with 10% ethyl acetate in petroleum ether to produce 5-chloro-6-(4-fluorophenyl)-2-(trifluoromethyl)-1H-1,3-benzodiazole as a white solid (50.7 mg, 38%).

1. concentrationThe resulting mixture was concentrated under vacuum
2. dissolutiondissolved in water (200 ml)
3. extractionextracted with dichloromethane (3×200 ml)
4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customto give a residue, which
7. customwas purified by a silica gel column with 5% to 10% ethyl acetate in petroleum ether

ORD record

ord-6b9becd389fa43259eedac5264aac369

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000187B2