反应详情

温度

90 °C

A suspension of optically-enriched (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one (38 mg, 0.107 mmol) in triethylamine (1.1 mL, 8.03 mmol) was degassed by bubbling with nitrogen for 30 min. To this was added ethynylbenzene (15 μl, 0.134 mmol) and triphenylphosphine (3.7 mg, 0.014 mmol). After bubbling 5 min longer, the reaction was treated with copper(I) iodide (0.408 mg, 2.14 μmol) and bis(triphenylphosphine)palladium(II) chloride (1.8 mg, 2.6 μmol), bubbled briefly with nitrogen, sealed, and heated at 90° C. for 5 h. The reaction was concentrated, dissolved in a minimum of dichloromethane, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→50% EtOAc/Hex) gave a mixture of the two regioisomers. This material was further purified by chiral prep HPLC (Chiralcel OD, 40% EtOH/heptane/0.1% DEA) to give 9.6 mg (23%). 1H NMR (CDCl3) δ: 8.49 (d, J=1.2 Hz, 1H), 7.76 (d, J=5.8 Hz, 1H), 7.58-7.67 (m, 2H), 7.51 (td, J=7.5, 1.5 Hz, 1H), 7.35-7.48 (m, 4H), 7.23-7.28 (m, 1H), 7.16 (ddd, J=9.8, 8.9, 0.8 Hz, 1H), 6.28 (br. s., 1H), 5.62 (d, J=5.8 Hz, 1H), 5.17 (d, J=5.8 Hz, 1H). 13C NMR (CDCl3) δ: 160.1, 158.4, 156.2, 140.8, 139.2, 135.3, 132.2, 131.4, 129.5, 128.6, 127.5, 125.2, 124.9, 124.5, 121.8, 116.2, 90.2, 87.3, 79.3, 56.6. 19F NMR (CDCl3) δ: −117.69 (d, J=8.7 Hz, 1F), −132.34 (d, J=8.7 Hz, 1F). Mass spec.: 377.2 (MH)+.

1. customwas degassed
2. customby bubbling with nitrogen for 30 min
3. customAfter bubbling 5 min longer
4. custombubbled briefly with nitrogen
5. customsealed
6. concentrationThe reaction was concentrated
7. dissolutiondissolved in a minimum of dichloromethane
8. additiondiluted with ethyl acetate
9. washwashed with brine
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated
12. customColumn chromatography (25%→50% EtOAc/Hex) gave
13. additiona mixture of the two regioisomers
14. customThis material was further purified by chiral prep HPLC (Chiralcel OD, 40% EtOH/heptane/0.1% DEA)
15. customto give 9.6 mg (23%)