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

(±)-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)+.

1. concentrationThe reaction was concentrated under a stream of nitrogen
2. dissolutiondissolved in methanol
3. customThe cartridge was flushed with several volumes of methanol which
4. washThe product was eluted with 2M ammonia in methanol
5. concentrationconcentrated
6. temperaturecooled to 0° C.
7. stirringThe resulting suspension was stirred at 0° C. for 5 min
8. customThe ice bath was removed
9. stirringstirring
10. waitcontinued for 1 h
11. customThe reaction was quenched by addition of 2M ammonia in methanol
12. concentrationconcentrated
13. dissolutionThe resulting residue was dissolved in a minimum of ethyl acetate
14. additionpoured into water
15. additionThe organics were diluted with several volumes of diethyl ether
16. washThe ethereal was washed with water (2×)
17. dry with materialbrine, dried over magnesium sulfate
18. concentrationconcentrated
19. customColumn chromatography (25%-->50% EtOAc/Hex) gave 25 mg (53%)

ORD record

ord-ff0851452f3e4e9baeb80e056aa2294b

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2