(3-Fluorophenyl)carbamic acid benzyl ester → 2-Oxazolidinone, 3-(m-fluorophenyl)-5-hydroxymethyl-

Temperatur

-78 °C

A solution of amine 91 (39.2 g, 160.0 mmol) in anhydrous THF (300 mL) was cooled to −78° C. in a dry-ice/acetone bath before a solution of n-butyl lithium (n-BuLi, 2.5 M solution in hexane, 70.4 mL, 176 mmol, 1.1 equiv) was dropwise added under N2. The resulting reaction mixture was subsequently stirred at −78° C. for 1 h before a solution of (R)-(−)-glycidyl butyrate (25.37 g, 24.6 mL, 176 mmol, 1.1 equiv) in anhydrous THF (100 mL) was dropwise added into the reaction mixture at −78° C. under N2. The resulting reaction mixture was stirred at −78° C. for 30 minutes (min) before being gradually warmed to room temperature for 12 h under N2. When TLC and high performance liquid chromatography/mass spectrometry (HPLC/MS) showed the reaction was complete, the reaction mixture was quenched with H2O (200 mL), and the resulting mixture was stirred at room temperature for 1 h before EtOAc (200 mL) was added. The two layers were separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with H2O (2×100 mL) and saturated aqueous NaCl (100 mL), dried over MgSO4, and concentrated in vacuo. White crystals precipitated from the concentrated solution when most of the solvent was evaporated. The residue was then treated with 20% EtOAc/hexane (100 mL) and the resulting slurry was stirred at room temperature for 30 min. The solids were collected by filtration and washed with 20% EtOAc/hexane (2×50 mL) to afford the desired (5R)-(3-(3-fluoro-phenyl)-5-hydroxymethyl-oxazolidin-2-one (alcohol 92, 24.4 g, 72.3% yield) as white crystals. This product was directly used in subsequent reactions without further purification. 1H NMR (300 MHz, DMSO-d6) δ 3.34–3.72 (m, 2H), 3.83 (dd, 1H, J=6.2, 9.0 Hz), 4.09 (t, 1H, J=12.0 Hz), 4.68–4.75 (m, 1H), 5.23 (t, 1H, J=5.6 Hz, OH), 6.96 (m, 1H), 7.32–7.56 (m, 3H). C10H10FNO3, LCMS (EI) m/e 212 (M++H).

1. additionwas dropwise added under N2
2. customThe resulting reaction mixture
3. additionwas dropwise added into the reaction mixture at −78° C. under N2
4. customThe resulting reaction mixture
5. temperaturebefore being gradually warmed to room temperature for 12 h under N2
6. customthe reaction mixture was quenched with H2O (200 mL)
7. stirringthe resulting mixture was stirred at room temperature for 1 h before EtOAc (200 mL)
8. additionwas added
9. customThe two layers were separated
10. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
11. washThe combined organic extracts were washed with H2O (2×100 mL) and saturated aqueous NaCl (100 mL)
12. dry with materialdried over MgSO4
13. concentrationconcentrated in vacuo
14. customWhite crystals precipitated from the concentrated solution when most of the solvent
15. customwas evaporated
16. additionThe residue was then treated with 20% EtOAc/hexane (100 mL)
17. stirringthe resulting slurry was stirred at room temperature for 30 min
18. filtrationThe solids were collected by filtration
19. washwashed with 20% EtOAc/hexane (2×50 mL)
20. customto afford the

ORD-Eintrag

ord-03ed6213c78e4a2eaa8202814c6698cb

Quelldatensatz

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07129259B2