4-Methoxy-2,2,6,6-tetramethylpiperidinyl-1-oxy → 1-(5,6-dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanone

Temperature

-10 °C

A 3-L 4-neck flask equipped with a thermocouple controller, an overhead mechanical stirrer, an addition funnel, and a nitrogen inlet/outlet adaptor was charged with 1-(5,6-dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol (91.0 g, 0.32 mol), 4-methoxy-TEMPO (14.3 g, 0.077 mol), and KBr (4 g, 0.0336 mol) in THF (900 mL). The brown homogenous solution was stirred for 15 min while cooling to −10° C. After cooling, NaOCl (670 ml) was added dropwise over a ½ h period. The reaction mixture was diluted with EtOAc (1.5 L) and H2O (1.5 L). When the effervescence ceased, the phases were split and the aqueous layer was back extracted with EtOAc (2 L). The combined organic layer was washed with brine (2 L); dried over Na2SO4, filtered and evaporated to dryness to yield a crude residue. The crude residue was purified by flash chromatography using SiO2 (1 kg) and 40% EtOAc/hexanes (24 L) and the product dried in vacuo for 18 h at 50° C. to yield 1-(5,6-dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanone as a yellow solid.

1. customA 3-L 4-neck flask equipped with a thermocouple controller, an overhead mechanical stirrer, an addition funnel, and a nitrogen inlet/outlet adaptor
2. temperatureAfter cooling
3. customthe phases were split
4. extractionthe aqueous layer was back extracted with EtOAc (2 L)
5. washThe combined organic layer was washed with brine (2 L)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customevaporated to dryness
9. customto yield a crude residue
10. customThe crude residue was purified by flash chromatography
11. customthe product dried in vacuo for 18 h at 50° C.

ORD record

ord-c4d9c108a96244fabb4a93e4cf007adc

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802865B2