反应详情

tert-Butyl (2R,5R)-2-ethynyl-5-(tert-butyldimethylsilyloxy-methyl)morpholine-4-carboxylate (2.75 g, 7.73 mmol), 5-fluoro-4-iodopyridin-3-amine (1.84 g, 7.73 mmol), bis(triphenylphosphine)palladium(II) chloride (0.380 g, 0.541 mmol), triethylamine (32.3 mL, 232 mmol), and copper(I) iodide (0.147 g, 0.773 mmol) were heated at 70° C. for 2 hours. The reaction was quenched with saturated aqueous KH2PO4 and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. Purification on silica gel (330 g) eluting with a gradient of 0-100% EtOAc/hexanes afforded the title compound (2.20 g, 12.9 mmol, 42% yield) as a viscous oil, MS (ESI): m/z=466.45 (MH+); 68% pure by LCMS, remainder is un-reacted 5-fluoro-4-iodopyridin-3-amine, taken onto next reaction as mixture.

1. customThe reaction was quenched with saturated aqueous KH2PO4
2. extractionthe mixture was extracted with ethyl acetate (×3)
3. dry with materialThe combined organic fractions were dried (MgSO4)
4. filtrationfiltered
5. customthe solvent was evaporated under reduced pressure
6. customPurification on silica gel (330 g)
7. washeluting with a gradient of 0-100% EtOAc/hexanes