Hydrochloric Acid → (S)-3,3-Difluoro-5-(hydroxymethyl)pyrrolidin-2-one

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.

1. concentrationThe reaction mixture was concentrated
2. dissolutionThe resulting residue was dissolved in THF (10 mL)
3. additionTEA (5 mL) was added
4. stirringThe resulting solution was stirred for 1 h
5. concentrationThe reaction mixture was concentrated
6. customto give a crude mixture
7. customPurification by flash column chromatography (hexanes/EtOAc)

ORD record

ord-fa90452dd1b449bf869294dd7425f290

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088793B2