Pivaloyl chloride → 4-Benzyl-3-(2-butyl-acryloyl)-oxazolidin-2-one

Temperature

-78 °C

2-n-butyl acrylic acid (9.90 g, 77.2 mmol, and 1 equiv.) is dissolved in dry THF (260 mL) and cooled to −78° C. under nitrogen. Hunig's base (17.5 mL, 100.4 mmol, 1.3 equiv.) and pivaloyl chloride (9.5 mL, 77.2 mmol, 1 equiv.) are added at such a rate that the temperature remains below −60° C. The mixture is stirred at −78° C. for 30 minutes, warmed to rt for 2 hours, and finally cooled back to −78° C. In a separate flask, (S)-(−)-4-benzyl-2-oxazolidinone (13.49 g, 77.24 mmol) is dissolved in dry THF (150 mL) and cooled to −78° C. under nitrogen. n-butyllithium (2.5 M solution in hexanes, 30.9 mL, 77.2 mmol, 1 equiv.) is added slowly at −78° C., and the mixture is stirred for 30 minutes at rt. The resulting anion is slowly transferred via a cannula into the original reaction vessel. The mixture is allowed to warm to rt and is stirred overnight at rt. The reaction is quenched with 1 M KHCO3, and the solvents are removed under reduced pressure. The residue is partitioned between EtOAc and water. The organic layer is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a yellow oil which is purified by FC (hexane:EtOAc=4:1) to yield the title compound A-3 as a white solid.

1. customremains below −60° C
2. temperaturewarmed to rt for 2 hours
3. temperaturefinally cooled back to −78° C
4. temperaturecooled to −78° C. under nitrogen
5. stirringthe mixture is stirred for 30 minutes at rt
6. temperatureto warm to rt
7. stirringis stirred overnight at rt
8. customThe reaction is quenched with 1 M KHCO3
9. customthe solvents are removed under reduced pressure
10. customThe residue is partitioned between EtOAc and water
11. washThe organic layer is washed with brine
12. dry with materialdried over anhydrous Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customto give a yellow oil which
16. customis purified by FC (hexane:EtOAc=4:1)

ORD record

ord-3475cf71194343e59ae7d1c558c319f1

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07148242B2