Acetic Acid → HCID 10704914, compound

Temperature

40 °C

The oxazolidinone 29 (4.2 g, 13.7 mmol) was dissolved in THF (15 mL) and was added dropwise over 15 min to a solution of potassium bis(trimethylsilyl)amide (20.1 mL, 0.69 M in THF, 13.9 mmol) at −78° C. After 45 min at −78° C., 2,4,6-triisopropylbenzenesulfonyl azide (4.9 g, 15.8 mmol) in THF (10 mL) at −78° C. was added in one portion to the enolate. After 5 min, glacial acetic acid (4.6 equiv, 3.8 g, 3.61 mL, 63.2 mmol) was added and the mixture was stirred at 40° C. for 1 h. Tetrahydrofuran was evaporated under reduced pressure and the residue was dissolved in a mixture of EtOAc and water. The organic phase was washed with saturated aqueous NaHCO3, followed by brine, dried (MgSO4), filtered and concentrated. The residual oil was dissolved in 75 mL of hexane/ethyl acetate (2/1). After 16 h at 25° C., the white precipitate was removed by filtration and the filtrate was concentrated to give an oily residue which was filtered through a pad of silica, washed with hexane/ethyl acetate (8/1). This material (crude 30, 1.3 g, 27%) was dissolved in THF/water (70 mL, 3/1) and H2O2 (4 equiv, 30%, 1.69 mL, 15 mmol) was added at 0° C. followed by LiOH·H2O (2.1 equiv, 0.33 g, 7.88 mmol). After 45 min, 10% aqueous Na2S2O3 (48 mL) and solid NaHCO3 (0.22 g) were added. The reaction mixture was concentrated and ca 50 mL of water was added. The aqueous phase was washed with chloroform (4 times), acidified at 0° C. with 15% HCl, and extracted with EtOAc (3 times). The combined EtOAc extracts were dried (MgSO4), filtered and concentrated to provide compound 31 (0.79 g, 90% from crude 30) as a white solid: mp 110-112° C.; [α]D2−36° (c 1.60, MeOH); 1H-NMR (400 MHz, CDCl3) δ 3.60 (s, 1H), 2.16-2.00 (m, 3H), 1.76-1.62 (m, 12H); 13C-NMR (100.6 MHz, CDCl3) δ 174.19, 72.51, 38.68, 37.50, 36.51, 28.19; FAB MS m/z: 236 (MH+); HRMS calcd for C12HI8N3O2 (MH+) 236.1399, found: 236.1389; Anal (C12H17N3O2) C, H, N.

1. waitAfter 5 min
2. customTetrahydrofuran was evaporated under reduced pressure
3. dissolutionthe residue was dissolved in a mixture of EtOAc and water
4. washThe organic phase was washed with saturated aqueous NaHCO3
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe residual oil was dissolved in 75 mL of hexane/ethyl acetate (2/1)
9. waitAfter 16 h at 25° C.
10. customthe white precipitate was removed by filtration
11. concentrationthe filtrate was concentrated
12. customto give an oily residue which
13. filtrationwas filtered through a pad of silica
14. washwashed with hexane/ethyl acetate (8/1)
15. dissolutionThis material (crude 30, 1.3 g, 27%) was dissolved in THF/water (70 mL, 3/1)
16. waitAfter 45 min
17. concentrationThe reaction mixture was concentrated
18. additionca 50 mL of water was added
19. washThe aqueous phase was washed with chloroform (4 times)
20. customacidified at 0° C. with 15% HCl
21. extractionextracted with EtOAc (3 times)
22. dry with materialThe combined EtOAc extracts were dried (MgSO4)
23. filtrationfiltered
24. concentrationconcentrated

ORD record

ord-68a4f8953e2f490491b95252e850710d

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06291640B1