Trimethylsilyl triflate → N-{3-[3,5-difluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide

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Reaction Steps

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).

Provenance & Evidence