反应详情

To a solution of 5.0 g (20.47 mmol) (2-amino-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester (Example 73, intermediate g) in 50 ml methanol, 2.21 g (22.57 mmol) cyclopentanecarbaldehyde (commercially available) were added. After stirring for 5 min. at room temperature, 3.2 g (20.5 mmol) p-chlorobenzoic acid and 2.5 ml (20.47 mmol) benzyl isocyanide (commercially available) were added. After stirring for 19 h, 38.38 ml (153.52 mmol) 4 M hydrochloric acid in dioxane were added dropwise over 5 min. After 5 h the solution was poured on 500 ml saturated aqueous sodium bicarbonate solution and the phases were separated. The organic layer was extracted three times with ethyl acetate and the combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and evaporated. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50). Light yellow foam (97%). MS (Turbo Spray): m/z=480.1 [M+H].

1. stirringAfter stirring for 19 h
2. customthe phases were separated
3. extractionThe organic layer was extracted three times with ethyl acetate
4. washthe combined organic layers were washed with water and brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by silica gel chromatography
9. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50)