反应详情

To a microwave vial was added N-[(3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-yl]propane-2-sulfonamide (124 mg, 0.340 mmol), phenylboronic acid (63.5 mg, 0.521 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos, 16.2 mg, 0.034 mmol), palladium(II) acetate (5.2 mg, 0.023 mmol) and potassium fluoride (99.6 mg, 1.71 mmol). The vial was capped, and purged three times with nitrogen/vacuum. A 1:1 mixture of degassed methanol/toluene (1.5 mL) was added and the reaction was subjected to microwave irradiation at 130° C. for 30 minutes. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate and saturated aqueous sodium chloride solution. The aqueous layer was extracted twice with ethyl acetate, and the organic layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Gradient: 10% to 25% ethyl acetate in heptane), to afford the title compound as a solid. Yield: 90 mg, 0.25 mmol, 73%. 1H NMR (400 MHz, CDCl3) δ 1.37 (d, J=6.8 Hz, 3H), 1.40 (d, J=6.8 Hz, 3H), 3.17 (septet, J=6.8 Hz, 1H), 3.76 (dd, J=8.6, 8.6 Hz, 1H), 4.01 (dd, J=10.6, 1.6 Hz, 1H), 4.16-4.30 (m, 3H), 4.84 (m, 1H), 5.09 (d, J=9.4 Hz, 1H), 6.97 (d, J=8.7 Hz, 2H), 7.34 (t, J=7.4 Hz, 1H), 7.44 (dd, J=7.6, 7.6 Hz, 2H), 7.55 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 16.48, 16.55, 54.27, 55.35, 70.29, 71.96, 75.87, 115.85, 126.65, 126.88, 128.34, 128.68, 135.11, 140.25, 155.93.

1. customThe vial was capped
2. custompurged three times with nitrogen/vacuum
3. additionA 1:1 mixture of degassed methanol/toluene (1.5 mL)
4. additionwas added
5. customirradiation at 130° C. for 30 minutes
6. customThe solvent was removed in vacuo
7. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium chloride solution
8. extractionThe aqueous layer was extracted twice with ethyl acetate
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by silica gel chromatography (Gradient: 10% to 25% ethyl acetate in heptane)