反应详情

To a suspension of 3.05 g (5.46 mmol) N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-(4,4-difluoro-cyclohexyl)-acetamide in 15 ml tetrahydrofuran and 10 ml water were added dropwise over 5 min. a solution of 2.29 g (54.57 mmol) lithium hydroxide monohydrate in 11.14 ml (109 mmol) 30% hydrogen peroxide solution and 10 ml water. The reaction mixture turned into a turbid solution and became slightly warm (cooled temporarily using an ice-bath). After stirring for 2 h the pH was adjusted to pH 4 using 12.48 ml (218 mmol) acetic acid. The resulting light yellow solution was extracted three times with ethyl acetate. The combined organic layers were washed twice with saturated aqueous sodium bicarbonate solution, brine, dried over magnesium sulfate, filtered and evaporated. The remaining yellow foam was treated with 100 ml tert-butyl methylether and the resulting light yellow suspension was filtered, washed with tert-butyl methyl ether and dried under high vacuum to give a first batch of compound (yellow solid). The mother liquor was purified on a preparative HPLC system (Phenomenex Gemini column) eluting with a gradient of acetonitrile and water. to give another batch of compound (colorless solid). Overall yield 49%. MS (Turbo Spray): m/z=441.3 [M+H].

1. temperaturebecame slightly warm (
2. temperaturecooled temporarily
3. extractionThe resulting light yellow solution was extracted three times with ethyl acetate
4. washThe combined organic layers were washed twice with saturated aqueous sodium bicarbonate solution, brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated
8. additionThe remaining yellow foam was treated with 100 ml tert-butyl methylether
9. filtrationthe resulting light yellow suspension was filtered
10. washwashed with tert-butyl methyl ether
11. customdried under high vacuum
12. customto give a first batch of compound (yellow solid)
13. customThe mother liquor was purified on a preparative HPLC system (Phenomenex Gemini column)
14. washeluting with a gradient of acetonitrile and water
15. customto give another batch of compound (colorless solid)