反应详情

Under a nitrogen atmosphere, add 3-(tert-butoxycarbonylamino-methyl)-6-chloropyridine (1 g, 4.12 mmol), cyclohexylacetylene (0.446 g, 4.12 mmol), dichlorobis(triphenylphosphine)-palladium (578 mg, 0.824 mmol), copper(I) iodide (157 mg, 0.824 mmol) and triethylamine (8.6 mL, 6.18 mmol) to THF (20 mL). Heat the mixture to reflux overnight. Cool the mixture to room temperature, and dilute with saturated aqueous NaHCO3 (50 mL) and EtOAc (50 mL). Separate the layers and extract the aqueous layer with EtOAc (4×30 mL). Wash the combined organic extracts with brine (20 mL), dry over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (120 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 6:1 gradient over 1.25 h, 80 mL/min) to obtain the desired intermediate as a colorless oil (0.71 g, 55%). MS (APCI+) m/z: 215 (M-Boc+H)+.

1. temperatureHeat the mixture
2. temperatureto reflux overnight
3. customSeparate the layers
4. extractionextract the aqueous layer with EtOAc (4×30 mL)
5. washWash the combined organic extracts with brine (20 mL)
6. dry with materialdry over Na2SO4
7. filtrationfilter
8. concentrationconcentrate in vacuo
9. customPurify the crude mixture by chromatography on silica gel (120 g, pre-packed cartridge)
10. washeluting with hexane/EtOAc (1:0 to 6:1 gradient over 1.25 h, 80 mL/min)