Hydrochloric Acid → (S)-3,3-Difluoro-5-(hydroxymethyl)pyrrolidin-2-one
Reaction equation
[F:1][C:2]1([F:13])[C:11](=[O:12])[N:5]2C(C)(C)[O:7][CH2:8][C@@H:4]2[CH2:3]1.Cl>CO.O1CCOCC1>[F:1][C:2]1([F:13])[CH2:3][C@@H:4]([CH2:8][OH:7])[NH:5][C:11]1=[O:12]Participants
5
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of (S)-6,6-difluoro-3,3-dimethyl-dihydropyrrolo[1,2-c]oxazol-5(1H,3H,6H)-one (1.35 g, 0.706 mmol) in methanol (10 mL) was added HCl in dioxane (2.65 mL, 4N) under ice-water bath and then stirred at RT overnight. The reaction mixture was concentrated. The resulting residue was dissolved in THF (10 mL) and TEA (5 mL) was added. The resulting solution was stirred for 1 h. The reaction mixture was concentrated to give a crude mixture. Purification by flash column chromatography (hexanes/EtOAc) gave (S)-3,3-difluoro-5-(hydroxymethyl)pyrrolidin-2-one (0.80 g 75%). LRMS (M+H+) m/z 152.2.