Acetic Acid → HCID 10704914, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence