反应详情

Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 25e, 800 mg, 1.36 mmol) was dissolved in N,N-dimethylformamide (52 mL). Cesium carbonate (1.1 g, 3.4 mmol) and 2-fluoroethyltosylat (445 mg, 2.04 mmol) were added. The mixture was stirred at room temperature for 3.5 hours, additional cesium carbonate (70 mg, 0.21 mmol) and 2-fluoroethyltosylate (28 mg, 0.13 mmol) were added and stirring was continued for 2.5 hours at room temperature and 17 hours at 5° C. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with diethyl ether and ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane 20 to 100% followed by dioxane in ethyl acetate 0 to 50%) to yield 670 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-fluoroethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

1. stirringstirring
2. waitwas continued for 2.5 hours at room temperature and 17 hours at 5° C
3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
4. extractionextracted with diethyl ether and ethyl acetate
5. washThe combined extracts were washed with brine
6. dry with materialdried over sodium sulfate
7. concentrationThe solution was concentrated under reduced pressure
8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane 20 to 100% followed by dioxane in ethyl acetate 0 to 50%)