1,1'-Carbonyldiimidazole → (4R,5R)-4-(5-bromopyridin-3-yl)-5-(3-methoxyphenyl)oxazolidin-2-one

Participants

Reaction Steps

Optically-enriched tert-butyl (1R,2R)-1-(5-bromopyridin-3-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamate (3.76 g, 4.44 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 40 mL) and stirred at room temperature for 1 h. The reaction was concentrated, dissolved in methanol, and loaded onto a strong cation exchange cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated. The resulting residue was suspended in tetrahydrofuran (40 mL), cooled to 0° C., and treated with carbonyldiimidazole (1.46 g, 9.00 mmol) in a single portion. The resulting suspension was stirred at 0° C. for 5 min. The ice bath was removed and stirring continued for 1 h. The reaction was re-cooled to 0° C., and treated with an additional portion of carbonyldiimidazole (500 mg) and stirred at room temperature for 1 h. The reaction was quenched by addition of 2M ammonia in methanol and concentrated. The resulting residue was purified by column chromatography (25%-->50% EtOAc/Hex) to give 660 mg (21%). 1H-NMR (CDCl3, 500 MHz) δ 8.69 (d, J=2.1, 1H), 8.39 (d, J=2.1, 1H), 7.92 (dd, J=2.1, 1.8, 1H), 7.34 (dd, J=7.9, 7.9, 1H), 6.95 (dd, J=8.6, 1.8, 1H), 6.77-6.91 (m, 3H), 5.22 (d, J=7.6, 1H), 4.82 (d, J=7.6, 1H), 3.82 (s, 3H). 13C-NMR (CDCl3, 126 MHz) δ 160.3, 158.9, 151.7, 146.4, 137.8, 136.7, 136.0, 130.5, 121.6, 118.1, 115.2, 111.4, 85.6, 62.2, 55.5. Mass spec.: 349.12 (MH)+.

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