1,1'-Carbonyldiimidazole → (4R,5R)-4-(6-bromopyridin-2-yl)-5-(3-methoxyphenyl)oxazolidin-2-one

Participants

Reaction Steps

(±)-tert-Butyl (1R,2R)-1-(6-bromopyridin-2-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamate (114 mg, 0.135 mmol) was dissolved in trifluoroacetic acid (10% in dichloromethane, 5 mL) and stirred at room temperature for 2 h. The reaction was concentrated under a stream of nitrogen, 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 (2 mL), cooled to 0° C., and treated with carbonyldiimidazole (43.7 mg, 0.27 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 quenched by addition of 2M ammonia in methanol and concentrated. The resulting residue was dissolved in a minimum of ethyl acetate and poured into water. The organics were diluted with several volumes of diethyl ether. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%-->50% EtOAc/Hex) gave 25 mg (53%). 1H-NMR (CDCl3, 500 MHz) δ 7.64 (dd, J=7.9, 7.6, 1H), 7.51 (d, J=7.9, 1H), 7.40 (d, J=7.6, 1H), 7.35 (dd, J=8.2, 8.2, 1H), 7.03 (m, 2H), 6.93 (m, 1H), 6.84 (bs, 1H), 5.60 (d, J=5.5, 1H), 4.91 (d, J=5.8, 1H), 3.85 (s, 3H). 13C-NMR (CDCl3, 126 MHz) δ 160.2, 159.9, 159.1, 142.6, 139.8, 139.7, 130.2, 128.2, 119.7, 117.8, 114.8, 111.0, 83.4, 64.4, 55.5. Mass spec.: 349.04 (MH)+.

Provenance & Evidence