Hydrogen Peroxide → HCID 29417677, compound

Participants

Reaction Conditions

Reaction Steps

NEt3 (15.4 mL, 110 mmol) was added to a stirred suspension of 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propanoic acid (Preparation 41, 30.0 g, 96.0 mmol) in anhydrous THF (300 mL) at 0° C. After 10 min, pivaloyl chloride (13.6 mL, 110 mmol) was added dropwise over 20 min and the mixture was stirred at 0° C. for 2 h. Meanwhile, n-BuLi (45.3 mL of a 2.5M solution in hexanes, 115 mmol) was added to a solution of (R)-(+)-4-benzyl-2-oxazolidinone (20.4 g, 115 mmol) in anhydrous THF (300 mL) at −78° C. The mixture was stirred at −78° C. to 20° C. over 2 h. The solution thus obtained was added dropwise to the abovementioned mixed anhydride solution at −78° C. The reaction was stirred at −78° C. for 1 h and then at 20° C. for 4 h, before being treated with H2O (300 mL). The THF was removed in vacuo, then the remainder was extracted with EtOAc (3×300 mL). The combined organic layers were washed with H2O, dried (Na2SO4), filtered, and concentrated in vacuo. Chromatographic separation (EtOAc-n-C6H14, 1:2 to 1:1) afforded two products: (1) (4R)-4-benzyl-3-[(2R)-2-[4-(methylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoyl]-1,3-oxazolidin-2-one: mp 139-141° C. (from Et2O-THF); (2) (4R)-4-benzyl-3-[(2S)-2-[4-(methylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoyl]-1,3-oxazolidin-2-one: m/z (APCI+)=472 [M+H]+. A solution of LiOH (1.5 g, 64 mmol) and 35% aqueous H2O2 (14.5 g, 128 mmol) in H2O (400 mL) was added dropwise over 40 min to a stirred solution of (4R)-4-benzyl-3-[(2R)-2-[4-(methylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoyl]-1,3-oxazolidin-2-one (15.1 g, 10.9 mmol) in THF-H2O (3:1, 1.6 L) at 0° C. The reaction was stirred at 0° C. for 1.5 h, then the remaining oxidant was destroyed with 10% aqueous Na2SO3. The mixture was washed with Et2O (4×300 mL), acidified with 10% aqueous HCl, and extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Trituration with Et2O-hexanes gave the title compound: mp 217° C.; the absolute configuration was determined by X-ray crystallographic analysis.

Provenance & Evidence