1,1'-Carbonyldiimidazole → (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one

Optically-enriched tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(2,5-difluorophenyl)-2-hydroxyethylcarbamate (253 mg, 0.283 mmol) was dissolved in trifluoroacetic acid (10% in dichloromethane, 10 mL) and stirred at room temperature overnight. In the morning, the reaction was concentrated and loaded onto a strong cation exchange cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The crude aminoalcohol was eluted with 2M ammonia in methanol and concentrated to give 53 mg as a solid. The crude solid was dissolved in tetrahydrofuran (5 mL), cooled to 0° C., and treated with carbonyldiimidazole (45.9 mg, 0.283 mmol). After 5 min, the ice bath was removed, and stirring continued for 1 h. The reaction was quenched by addition of 2M ammonia in methanol. The reaction was concentrated and purified by column chromatography (25%→50% EtOAc/Hex) to give 20 mg (9.5%). Mass spec.: 373.1 (MH)+.

1. concentrationIn the morning, the reaction was concentrated
2. customThe cartridge was flushed with several volumes of methanol which
3. washThe crude aminoalcohol was eluted with 2M ammonia in methanol
4. concentrationconcentrated
5. customto give 53 mg as a solid
6. temperaturecooled to 0° C.
7. waitAfter 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. concentrationThe reaction was concentrated
13. custompurified by column chromatography (25%→50% EtOAc/Hex)
14. customto give 20 mg (9.5%)

ORD record

ord-291bf16a2a6140eca217eb14ccf06cd6

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2