Pivaloyl chloride → (4S)-4-benzyl-3-[(2E)-3-phenylprop-2-enoyl]-1,3-oxazolidin-2-one

Temperature

0 °C

A solution of 222 g (1.5 mol) of trans-cinnamic acid and 250 mL (1.77 mol) of TEA in 3 L of THF at −78° C. was treated with 200 mL of trimethylacetyl chloride maintaining the internal temperature at less than −65° C. The resulting mixture was warmed to 0° C., then cooled to −78° C. In a separate flask, a solution of 4-(S)-benzyl-oxazolidin-2-one in 2.05 L of THF at −20° C. was treated with 660 mL of 2.5 M n-butyllithium in hexanes over 45 min. The resulting turbid mixture was cooled to −78° C. and then transferred via cannula to the flask containing the mixed anhydride. The resulting mixture was allowed to warm to rt and was stirred for 20 h. The reaction was quenched with 300 mL of sat'd NH4Cl; the resulting mixture was partitioned between EtOAc and H2O and the layers were separated. The organic layer was dried over MgSO4. The aqueous layer was extracted with 2×EtOAc; the extracts were dried and all of the organic extracts were combined. Partial concentration in vacuo caused precipitation of a solid; the mixture was diluted with hexanes and allowed to stand at rt for 1.5 h. The precipitate was filtered and dried to afford the title compound: 1H NMR (500 MHz, CDCl3) δ2.86 (dd, J=13.5, 9.5, 1H), (3.38, J=13.5, 3.5, 1H), 4.20-4.27 (m, 2H), 4.78-4.83 (m, 1H), 7.24-7.42 (5H), 7.63-7.65 (m, 1H), 7.92 (app d, J=2.5, 1H).

1. temperaturecooled to −78° C
2. temperatureThe resulting turbid mixture was cooled to −78° C.
3. temperatureto warm to rt
4. customThe reaction was quenched with 300 mL of sat'd NH4Cl
5. customthe resulting mixture was partitioned between EtOAc and H2O
6. customthe layers were separated
7. dry with materialThe organic layer was dried over MgSO4
8. extractionThe aqueous layer was extracted with 2×EtOAc
9. customthe extracts were dried
10. concentrationPartial concentration in vacuo
11. customprecipitation of a solid
12. additionthe mixture was diluted with hexanes
13. waitto stand at rt for 1.5 h
14. filtrationThe precipitate was filtered
15. customdried

ORD record

ord-bae75ed21d874f59b2be43db6ab05d4f

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06531484B2