Triphenylmethane → (S)-4-Benzyl-2-oxazolidinone

Participants

Reaction Conditions

Reaction Steps

To a solution of 3,3-dimethyl-3-phenyl propionic acid (10 g, 57 mmol, from Reference Example 22) in anhydrous tetrahydrofuran (120 mL) is added under inert atmosphere triethylamine (10 mL) and the mixture is cooled to −78° C. in a dry-ice acetone bath. Pivaloyl chloride (7.4 mL, 60 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-benzyl-2-oxazolidinone (9.9 g, 56 mmol) in anhydrous tetrahydrofuran (130 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, 40 mL, 64 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 and at 0° C. for 1 hour. Water (100 mL) is added and stirring is continued for 15 minutes. The aqueous phase is extracted thrice with diethyl ether. The combined extracts are washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over sodium sulfate, decanted, and concentrated under reduced pressure to afford 20 g of a white paste. The crude material is purified by flash chromatography (ethyl acetate/hexanes) to afford 11 g (56%) of a flocculent white solid. MS (ES+): (M+H)=338.1

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