反应详情

In a 1 mL scint vial, a suspension of optically-enriched (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one (20 mg, 0.054 mmol), and ethynylbenzene (0.014 mL, 0.129 mmol) in triethyl amine (1.5 mL) was purged with nitrogen for 30 min. Triphenylphosphine (3.7 mg, 0.014 mmol) was added and the suspension stirred for 5 min. To this was added copper (I) iodide (0.408 mg, 2.144 μmol), and bis(triphenylphosphine)palladium(II) chloride (1.8 mg, 2.6 μmol). The vial was purged with nitrogen for an additional 5 min, capped, and immersed in a 90° C. bath for 5 h. The reaction was cooled to room temperature and concentrated. The resulting residue was dissolved in dichloromethane and poured into water. The mixture was diluted with ethyl acetate, washed with water, brine, dried over magnesium sulfate, and concentrated. The material was purified first by reversed phase HPLC (TFA/MeOH/sunfire column) to give an optically enriched mixture of regioisomers. The material was further purified by chiral prep HPLC (Chiralpak AD, A=heptane/0.1% DEA, B=ethanol, 40%→60% over 35 min) to give the title compound (3.4 mg). 1H NMR (CDCl3) δ: 8.52 (d, J=0.9 Hz, 1H), 7.75 (d, J=5.8 Hz, 1H), 7.63 (dd, J=7.3, 2.1 Hz, 2H), 7.38-7.44 (m, 3H), 7.23-7.27 (m, 1H), 7.11-7.17 (m, 2H), 5.79 (br. s., 1H), 5.64 (d, J=5.5 Hz, 1H), 5.08 (d, J=5.5 Hz, 1H). 1H NMR (CDCl3) δ: 8.51 (d, J=0.9 Hz, 1H), 7.73 (d, J=5.5 Hz, 1H), 7.63 (dd, J=7.6, 1.8 Hz, 2H), 7.39-7.46 (m, 3H), 7.23-7.27 (m, 1H), 7.10-7.16 (m, 2H), 5.95 (br. s., 1H), 5.61 (d, J=5.5 Hz, 1H), 5.13 (d, J=5.8 Hz, 1H). Mass spec.: 395.2 (MH)+.

1. customwas purged with nitrogen for 30 min
2. customThe vial was purged with nitrogen for an additional 5 min
3. customcapped
4. customimmersed in a 90° C.
5. customfor 5 h
6. concentrationconcentrated
7. dissolutionThe resulting residue was dissolved in dichloromethane
8. additionpoured into water
9. additionThe mixture was diluted with ethyl acetate
10. washwashed with water, brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated
13. customThe material was purified first by reversed phase HPLC (TFA/MeOH/sunfire column)
14. customto give
15. additionan optically enriched mixture of regioisomers
16. customThe material was further purified by chiral prep HPLC (Chiralpak AD
17. customover 35 min