Hydrochloric Acid → 1-(5,6-dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol

Temperature

100 °C

A 1-L 4-neck flask equipped with a thermocouple controller, an overhead mechanical stirrer, a condenser, and a nitrogen inlet/outlet adaptor was charged with 4,5-dichloro-1,2-phenylenediamine (71.3 g, 0.403 mol), trifluorolactic acid (87.0 g, 0.604 mol) and 4N HCl (340 mL). The reaction mixture was heated for 18 h at reflux (100° C.). The resulting solution was cooled to room temperature and then diluted with EtOAc (1 L) and H2O (1 L). The solution was slowly treated with NaHCO3 (500 g) until pH 8-9. After the effervescence ceased, the phases were split and aqueous layer was back extracted with EtOAc (3×1 L). The combine organic phase was washed with H2O (1 L) and brine (1 L); dried over MgSO4, filtered and evaporated to dryness to yield a crude residue. The crude residue was purified by flash chromatography using SiO2 (2 kg) and 10% EtOAc/CH2Cl2 (2 L) and 20% EtOAc/CH2Cl2 (32 L) and the product dried in vacuo for 18 h at 60° C. to yield the title compound as a brownish solid.

1. customA 1-L 4-neck flask equipped with a thermocouple controller, an overhead mechanical stirrer, a condenser, and a nitrogen inlet/outlet adaptor
2. temperatureThe reaction mixture was heated for 18 h
3. temperatureThe resulting solution was cooled to room temperature
4. customthe phases were split
5. extractionaqueous layer was back extracted with EtOAc (3×1 L)
6. washThe combine organic phase was washed with H2O (1 L) and brine (1 L)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated to dryness
10. customto yield a crude residue
11. customThe crude residue was purified by flash chromatography
12. customthe product dried in vacuo for 18 h at 60° C.

ORD record

ord-9ccfad4d265847d4b649346834b663c7

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802865B2