反应详情

A suspension of aryl boronic acid 120 (25.0 g, 64.30 mmol, 1.45 equiv) in a mixture of toluene (120 mL), EtOH (40 mL), and water (40 mL) was treated with (5S)—N-[3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 108 (16.80 g, 44.44 mmol, prepared as described in Example 1, above) and solid K2CO3 (18.40 g, 133.4 mmol, 3.0 equiv) at room temperature. The resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(PPh3)4 (2.57 g, 2.23 mmol, 0.05 equiv). The resulting reaction mixture was degassed three times under a steady stream of argon before being warmed to reflux for 8 h. When TLC and HPLC/MS showed the reaction was complete, the reaction mixture was cooled to room temperature before being poured into water (300 mL) and ethyl acetate (EtOAc, 300 mL). The two layers were separated, and the organic phase was washed with water (60 mL) and saturated aqueous NaCl (2×50 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The product was recrystallized from EtOAc/hexanes and dried in vacuo to afford the desired (5S)-{4′-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl ester 121 (21.2 g, 61.5% yield for three steps) as an off-white powder.

1. customThe resulting reaction mixture
2. customwas degassed three times under a steady stream of argon
3. customThe resulting reaction mixture
4. customwas degassed three times under a steady stream of argon
5. temperaturebefore being warmed
6. temperatureto reflux for 8 h
7. additionbefore being poured into water (300 mL) and ethyl acetate (EtOAc, 300 mL)
8. customThe two layers were separated
9. washthe organic phase was washed with water (60 mL) and saturated aqueous NaCl (2×50 mL)
10. dry with materialdried over anhydrous Na2SO4
11. concentrationconcentrated in vacuo
12. customThe product was recrystallized from EtOAc/hexanes
13. customdried in vacuo