Pivaloyl chloride → HCID 57991875, compound

Temperature

-78 °C

To a solution of (E)-4-(tert-butyldimethylsilyloxy)but-2-enoic acid (18.0 g, 83.6 mmol) (prepared as described in Angewandte Chemie, International Edition (2002), 41(9), 1603-1607) in 400 mL of THF was added TEA (13.2 mL, 95 mmol). The mixture was chilled to −78° C. Pivaloyl chloride (10.2 mL, 83 mmol) (commercially available from Aldrich, Milwaukee, Wis.) was added. After 10 minutes, the mixture was warmed to room temperature and stirred for 45 minutes. The mixture was then chilled to −78° C. In a separate flask, (S)-4-phenyloxazolidin-2-one (12.3 g, 79 mmol) was taken up in 125 mL of THF and chilled to −78° C. n-Butyllithium (32 mL, 2.5 M in hexanes)(commercially available from Acros Organics (Order Number 30385)) was added to the (S)-4-phenyloxazolidin-2-one mixture, and the mixture was stirred for 20 minutes. The metallated oxazolidinone was then cannulated into the pivaloyl anhydride mixture. The combined mixture was then warmed to 0° C. and stirred for 1 hour. The reaction was quenched with 250 mL of aq NH4Cl and diluted with 250 mL of water. The mixture was extracted with EtOAc (2×250 mL) and the combined organic extracts were washed with brine (150 mL) and dried over MgSO4. Filtration and concentration under reduced pressure afforded a yellow solid that was recrystallized from DCM/hexanes to afford (S,E)-3-(4-(tert-butyldimethylsilyloxy)but-2-enoyl)-4-phenyloxazolidin-2-one (17.8 g, 62%) as a white solid. 1H NMR (400 MHz, CDCl3): ppm 7.46 (dt, J=2.1, 15.1 Hz, 1H), 7.31-7.20 (m, 5H), 7.02 (dt, J=3.4, 15.3 Hz, 1H), 5.40 (dd, J=3.9, 8.6 Hz, 1H), 4.61 (t, J=8.8 Hz, 1H), 4.19 (dd, J=3.9 Hz, 8.8 Hz, 1H), 0.85 (s, 9H), 0.00 (s, 6H). 2H were obscured.

1. addition) was added
2. temperaturethe mixture was warmed to room temperature
3. temperatureThe mixture was then chilled to −78° C
4. stirringthe mixture was stirred for 20 minutes
5. temperatureThe combined mixture was then warmed to 0° C.
6. stirringstirred for 1 hour
7. customThe reaction was quenched with 250 mL of aq NH4Cl
8. additiondiluted with 250 mL of water
9. extractionThe mixture was extracted with EtOAc (2×250 mL)
10. washthe combined organic extracts were washed with brine (150 mL)
11. dry with materialdried over MgSO4
12. filtrationFiltration and concentration under reduced pressure
13. customafforded a yellow solid
14. customthat was recrystallized from DCM/hexanes

ORD record

ord-e5c4b34eb65844c58220f42bbf4db4e5

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919504B2