Triethylamine → (R)-3-(2,5-difluoropyrimidin-4-yl)-4-((S)-1-fluoroethyl)oxazolidin-2-one

Temperature

0 °C

To a round bottom flask containing a solution of (R)-3-(2,5-difluoropyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one (4.64 g, 18.9 mmol) in Acetonitrile (63 mL) cooled to 0° C. was added perfluorobutanesulfonyl fluoride (10.2 mL, 56.8 mmol) followed by the addition of triethylamine trihydrofluoride (9.2 mL, 56.8 mmol) and triethylamine (23.7 mL, 170 mmol). The resulting reaction mixture allowed to stir at 0° C. for 4 hr. The reaction mixture was then diluted with water and the aqueous mixture was extracted with EtOAc. The organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided a white crystalline of (R)-3-(2,5-difluoropyrimidin-4-yl)-4-((S)-1-fluoroethyl)oxazolidin-2-one (2.24 g, 8.97 mmol, 47% yield). 1H NMR (400 MHz, CDCl3) 8.50 (s, 1H), 5.00-5.25 (m, 1H), 4.75-4.92 (m, 1H), 4.54-4.68 (m, 2H), 1.39 (dd, J=23.1, 7.0 Hz, 3H). LCMS m/z 248.0 (M+H)+, Rt 0.52 min.

1. customThe resulting reaction mixture
2. extractionthe aqueous mixture was extracted with EtOAc
3. washwashed with water, brine
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated onto silica gel

ORD record

ord-9da1ac267c7f4cb2ae27adafc2ed6cc5

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434719B2