Triethylamine → (R)-4-benzyl-3-[2-(4-methoxy-3-methyl-phenyl)-acetyl]-oxazolidin-2-one

온도

0 °C

To a solution of (4-methoxy-3-methyl-phenyl)-acetic acid (5.04 g, 27.97 mmol) and triethylamine (3.9 mL, 27.97 mmol) in anhydrous tetrahydrofuran (100 mL) under nitrogen at −78° C. was added trimethylacetyl chloride (3.44 mL, 27.97 mmol). The reaction mixture was stirred at −78° C. for 10 minutes, 0° C. for 1 hour, then re-cooled to −78° C. At the same time, to a separate flask charged with a solution of (R)-(+)-4-benzyl-2-oxazolidinone (4.96 g, 27.97 mmol) in anhydrous tetrahydrofuran (100 mL) under nitrogen at −78° C. was added dropwise a solution of n-butyllithium (14 mL, 28 mmol, 2 M in hexanes). The second reaction mixture was stirred at −78° C. for 20 minutes, then transferred via cannula into the first reaction flask containing the mixed anhydride at −78° C. The reaction mixture was stirred at 0° C. for 1 hour, then warmed to room temperature and stirred for 18 hours. The mixture was quenched with saturated aqueous ammonium chloride solution (200 mL), concentrated to about half of its original volume under reduced pressure to remove tetrahydrofuran. The remaining mixture was extracted with ethyl acetate (2×250 mL). The organic layers were separated, combined, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography over silica gel eluted with 1:1 ethyl acetate/hexanes to give (R)-4-benzyl-3-[2-(4-methoxy-3-methyl-phenyl)-acetyl]-oxazolidin-2-one as a pale yellow oil (8.5 g, 89%).

1. temperaturere-cooled to −78° C
2. customThe second reaction mixture
3. stirringwas stirred at −78° C. for 20 minutes
4. stirringThe reaction mixture was stirred at 0° C. for 1 hour
5. temperaturewarmed to room temperature
6. stirringstirred for 18 hours
7. customThe mixture was quenched with saturated aqueous ammonium chloride solution (200 mL)
8. concentrationconcentrated to about half of its original volume under reduced pressure
9. customto remove tetrahydrofuran
10. extractionThe remaining mixture was extracted with ethyl acetate (2×250 mL)
11. customThe organic layers were separated
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by chromatography over silica gel
15. washeluted with 1:1 ethyl acetate/hexanes

ORD 기록

ord-4622be6407114a45ba74e0dc37d3b648

출처 데이터셋

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07427635B2