Hydrochloric Acid → (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one

Temperature

45 °C

To a solution of optically-enriched tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(2-fluorophenyl)-2-hydroxyethylcarbamate (93 mg, 0.108 mmol) in dichloromethane (2 mL) at room temperature was added hydrogen chloride (4M in dioxane, 2 mL, 8 mmol). The reaction was warmed to 45° C. and held at that temperature for 1 h. The reaction was concentrated. The reaction was concentrated twice more from tetrahydrofuran. The resulting residue was suspended in tetrahydrofuran (2 mL), cooled to 0° C., and treated with diethylisopropylamine (0.038 mL, 0.217 mmol) and carbonyldiimidazole (26.3 mg, 0.162 mmol). After 5 min, the ice bath was removed and stirring continued for 3 h. The reaction was quenched by addition of 2M ammonia in methanol and concentrated. The resulting residue was suspended in dichloromethane, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→50% EtOAc/Hex) gave 37.8 mg (49%) as a colorless film. HNMR showed that it was a 1:1 mixture of regioisomers. The mixture was used without separation. Mass spec.: 355.0 (MH)+.

1. concentrationThe reaction was concentrated
2. concentrationThe reaction was concentrated twice more from tetrahydrofuran
3. temperaturecooled to 0° C.
4. waitAfter 5 min
5. customthe ice bath was removed
6. waitcontinued for 3 h
7. customThe reaction was quenched by addition of 2M ammonia in methanol
8. concentrationconcentrated
9. additiondiluted with ethyl acetate
10. washwashed with brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated
13. customColumn chromatography (25%→50% EtOAc/Hex) gave 37.8 mg (49%) as a colorless film
14. additiona 1:1 mixture of regioisomers
15. customThe mixture was used without separation

ORD record

ord-fc3b98c5db1647c0aedbd6ad154a3986

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2