77510-50-0

34368-52-0

77510-50-0

General procedure for the synthesis of (R)-3-hydroxypyrrolidinone from (S)-3-hydroxy-2-pyrrolidinone: To a mixture of (S)-3-hydroxy-2-pyrrolidinone (5.100 g, 50.4 mmol, 1.0 eq.) and 4-nitrobenzoic acid (9.273 g, 55.5 mmol. 1.1 eq.) to a mixture of triphenylphosphine (26.461 g, 100.9 mmol, 2.0 eq.). Subsequently, dipropyl azodicarboxylate (14.898 mL, 75.7 mmol, 1.5 equiv) was added dropwise under external cooling in a cold water bath. The reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, the mixture was concentrated in vacuum to give the crude product. Methanol (130 mL) and potassium carbonate (0.38 g) were added to the crude product and stirred at room temperature for 8 hours. The reaction mixture was diluted with dichloromethane and filtered through diatomaceous earth. The diatomaceous earth bed was washed with a 1% dichloromethane solution of methanol. The filtrates were combined and concentrated to dryness. The residue was partitioned between ethyl acetate and dilute hydrochloric acid aqueous solution (20 mL, 9:1) and stirred for 15 minutes. The organic and aqueous layers were separated and the aqueous layer was washed three times with ethyl acetate. The aqueous layer was concentrated to dryness to give a solid residue. The crude product was washed with a dichloromethane solution (3 x 50 mL) of 1-2% methanol, dried over anhydrous sodium sulfate, filtered and concentrated to give a brown oil (3.3 g, 60% yield). The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3): δ 4.32-4.27 (t, 1H, J = 8.5 Hz), 3.36-3.19 (m, 2H), 2.48-2.40 (m, 1H), 2.07-1.93 (m, 1H), 1.16-1.14 (d, 1H, J = 6.3 Hz).