HCID 90054371, compound → (R)-3,3-difluoro-5-(hydroxymethyl)pyrrolidin-2-one

Temperature

115 °C

To a solution consisting of (R)-6,6-difluoro-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one (intermediate 6, 12.5 g, 65.4 mmol) in water-1,4-dioxane (300 mL, 1:1 v/v) was added Amberlite IR-120H* (6.23 g). The reaction mixture was heated to 115° C. for 6 hours and was subsequently filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure, using toluene and ethanol additives to help drive off water, to provide a residue. The residue was washed with diethyl ether to afford the title compound as a tan solid (8.8 g; 89%), which was carried on without further purification; TLC Rf 0.25 (solvent system: 70:30 v/v ethyl acetate:hexanes). *Amberlite IR-120H ion-exchange resin, strongly acid gel-type resin with sulfonic acid functionality, CAS: 39389-20-3.75 g of Amberlite was washed and decanted three times with deionized water. The fourth wash was filtered using suction filtration and the semi-dry resin was quickly washed with 2-propanol then diethyl ether. The resin was dried to give 54 g of free flowing dark brown bead resin.

1. additionwas added Amberlite IR-120H* (6.23 g)
2. filtrationwas subsequently filtered through Celite
3. washwashed with methanol
4. concentrationThe filtrate was concentrated under reduced pressure
5. customto provide a residue
6. washThe residue was washed with diethyl ether

ORD record

ord-304265ac1c9b487ab1c8b4e4097f052f

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440919B2