Ethyl Acetate → (S)-1-(6-Chloro-5-fluoropyridin-3-yl)ethane-1,2-diol

Temperature

25 °C

To a solution of 112 (5.00 g, 31.75 mmol) in water (162 mL) and tert-butanol (162 mL) cooled to 0° C. with an ice bath was added AD-mix a (54.6 g, Sigma-Aldrich) to form a reaction mixture. With the bath ice left in place, the reaction mixture was allowed to warm to a temperature of about 25° C. After 16 hrs, excess solid sodium sulfite (60 g) was added and the resulting slurry was allowed to stir at a temperature of about 25° C. for 30 min. The mixture was extracted twice with EtOAc. The organic portions were combined, washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The resulting mixture was chromatographed on a silica gel column eluted with a gradient of from 50:50 EtOAc:hexanes to 100% EtOAc to provide 5.39 g of 113 as a white solid (89% yield). 1H NMR (CDCl3) δ: 2.16 (1H, t, J=5.60 Hz), 2.88 (1H, d, J=3.54 Hz), 3.66 (1H, m), 3.84 (1H, m), 4.91 (1H, m), 7.59 (1H, dd, J=1.61, 8.73 Hz), 8.29 (1H, d, J=1.88 Hz). LC/MS (M+1): m/z=192.

1. additionwas added AD-mix a (54.6 g, Sigma-Aldrich)
2. customto form a reaction mixture
3. waitWith the bath ice left in place
4. extractionThe mixture was extracted twice with EtOAc
5. washwashed with brine
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. customThe resulting mixture was chromatographed on a silica gel column
9. washeluted with a gradient of from 50:50 EtOAc

ORD record

ord-26bef4ae329a41c7ac790291a005fcda

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273043B2