Potassium Carbonate → HCID 86699568, compound

To a solution of 2-chloro-4-(trifluoromethyl)phenol (2 g, 10.18 mmol) in DMSO (250 ml) was added potassium carbonate (4.2 g, 30.17 mmol). The resulting solution was stirred overnight at room temperature, then 4,5-dichloro-2-nitroaniline (2.1 g, 10.14 mmol) was added. The resulting solution was stirred for an additional overnight at 90° C. and then quenched with water (1000 ml) and extracted with ethyl acetate (3×300 ml). The combined organic layers were washed with saturated aqueous brine (3×1000 ml), dried by anhydrous sodium sulfate and concentrated under vacuum to give a residue that was purified by a silica gel column, eluting with 1% to 1.5% ethyl acetate in petroleum ether to produce 4-chloro-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitroaniline as a yellow solid (450 mg, crude). Next, to a solution of 4-chloro-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitroaniline (450 mg, crude) in ethanol (10 ml) was added hydrochloric acid (conc) (0.484 ml) and Zn (478 mg, 7.35 mmol) in several batches at room temperature. The resulting solution was stirred for 10 min at room temperature and 2 h at 80° C. The reaction was concentrated under vacuum and dissolved in water (200 ml), pH adjusted to 8 with potassium 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 Prep-HPLC to produce 4-chloro-5-[2-chloro-4-(trifluoromethyl)phenoxy]benzene-1,2-diamine as a off-white solid (150 mg, 61%). Finally, a solution of 4-chloro-5-[2-chloro-4-(trifluoromethyl)phenoxy]benzene-1,2-diamine (50 mg, 0.15 mmol) in trifluoroacetic acid (5 ml) and conc. HCl (1 ml) was refluxed overnight. The reaction was then quenched with water (100 ml), pH value adjusted to 8 with sodium bicarbonate 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 Prep-TLC with 12.5% ethyl acetate in petroleum ether to produce 5-chloro-6-[2-chloro-4-(trifluoromethyl)phenoxy]-2-(pentafluoroethyl)-1H-1,3-benzodiazole as a white solid (36.4 mg, 53%).

1. stirringThe resulting solution was stirred for an additional overnight at 90° C.
2. customquenched with water (1000 ml)
3. extractionextracted with ethyl acetate (3×300 ml)
4. washThe combined organic layers were washed with saturated aqueous brine (3×1000 ml)
5. dry with materialdried by anhydrous sodium sulfate
6. concentrationconcentrated under vacuum
7. customto give a residue that
8. customwas purified by a silica gel column
9. washeluting with 1% to 1.5% ethyl acetate in petroleum ether

ORD record

ord-4842137ae9d0489ea898a5371cc1551d

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000187B2