反应详情

N-[3-(4-Amino-3,5-difluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (0.745 g, 2.61 mmol) and hydroxymethylbenzotriazole (0.390 g, 2.61 mmol) are dissolved in dry EtOH (2.0 mL). This resulting solution is refluxed for 5 h, solvent is removed under vacuum, and the resulted aminal intermediate dried under high vacuum. Danishefsky's diene (75.3 mg, 0.43 mmol) is added with stirring to the suspension of above aminal intermediate (0.091 g, 0.21 mmol) in THF (3 mL) at 0° C., followed by trimethylsilyl triflate (ca. 20 mL). The resulting mixture is allowed to warm up to r.t. over 2 h. Sat. aq. NaHCO3 (10 mL) is added, and the mixture extracted with excess EtOAc several times. Solvent is removed under vacuum, and the crude product purified by PTLC (5% MeOH in DCM) followed by RP HPLC (gradient 0–60% of MeCN—water). MS (m/z): 366 [M+H]+. 1H NMR (300 MHz, CDCl3) δ 1.90 (s, 3H), 2.50–2.54 (m, 2H), 3.53–3.64 (m, 2H), 3.84–3.92 (m, 3H), 4.22 (t, 1H, J=9.3 Hz), 4.81–4.89 (m, 1H), 5.04 (d, 1H, J=7.8 Hz), 7.25–7.29 (m, 1H) 7.39–7.51 (m, 3H).

1. temperatureThis resulting solution is refluxed for 5 h
2. customsolvent is removed under vacuum
3. dry with materialthe resulted aminal intermediate dried under high vacuum
4. extractionthe mixture extracted with excess EtOAc several times
5. customSolvent is removed under vacuum
6. customthe crude product purified by PTLC (5% MeOH in DCM)