Triphenylmethane → (4S)-4-(propan-2-yl)-1,3-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 3,3-dimethyl-3-phenyl propionic acid (2.1 g, 12 mmol, from Reference Example 22) in anhydrous tetrahydrofuran (24 mL) is added under inert atmosphere triethylamine (2.0 mL) and the mixture is cooled to −78° C. in a dry-ice acetone bath. Pivaloyl chloride (1.5 mL, 13 mmol) is added dropwise, causing the immediate formation of a white precipitate. The reaction mixture is allowed to sit for 15 minutes at −78° C. and is then stirred at 0° C. in an ice-water bath. In a separate flask, a solution of (S)-4-isopropyl-2-oxazolidinone (1.5 g, 12 mmol) in anhydrous tetrahydrofuran (27 mL) is prepared under inert atmosphere and cooled to −35° C. in a dry-ice/acetone bath. A small amount of triphenylmethane (<5 mg) is added as an indicator of deprotonation. n-Butyllithium (1.6 M solution in hexanes, 7.7 mL, 12 mmol) is added dropwise via syringe. After 30 minutes of stirring at 0° C., the flask containing the mixed anhydride is re-cooled to −78° C. in a dry-ice/acetone bath. The solution of the lithium anion of the oxazolidinone is added to the mixed anhydride solution via cannula. The source flask is washed twice with tetrahydrofuran (4 mL×2) and these washings are also transferred via cannula to the mixed anhydride solution. The reaction mixture is stirred at −78° C. for 1 hour, 0° C. for 1 hour, and allowed to warm to room temperature overnight. The following morning, water (˜15 mL) is added and stirring is continued for 20 minutes. The aqueous phase is extracted thrice with diethyl ether. The combined extracts are washed with saturated aqueous sodium chloride, dried over sodium sulfate, decanted, and concentrated under reduced pressure to afford (3.6 g, >100% crude) of a pale yellow oil. The crude material is purified by flash chromatography (ethyl acetate/hexanes) to afford 1.5 g (44%) of a clear, colorless oil. MS (ES+): (M+H)=290.0

Provenance & Evidence