反应详情

Dissolve 2-chloro-3-iodopyridine (4.00 g, 16.74 mmol) in anhydrous toluene (25 mL). Add piperazine-1-carboxylic acid t-butyl ester (2.96 g, 15.90 mmol), followed by palladium acetate (0.113 g, 0.50 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.313 g, 0.502 mmol), triethylamine (0.034 g, 0.047 mL, 0.335 mmol) and cesium carbonate (27.3 g, 83.7 mmol). Heat at reflux for 18 hr. Concentrate and partition the residue between DCM and a saturated solution of sodium bicarbonate. Extract the aqueous phase twice with DCM and once with ethyl acetate. Dry the combined organic extracts (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes), to give 4-(2-Chloropyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (54%). MS (ES): m/z=298 [M+H].

1. temperatureHeat
2. temperatureat reflux for 18 hr
3. concentrationConcentrate
4. custompartition the residue between DCM
5. extractionExtract the aqueous phase twice with DCM
6. dry with materialDry the combined organic extracts (sodium sulfate)
7. filtrationfilter
8. concentrationconcentrate
9. custompurify
10. wash(silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes)