Hydrochloric Acid → (1R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethan-1-ol

To a −78° C. toluene (25 mL)/dichloromethane (25 mL) solution of 2,2,2,4′-tetrafluoroacetophenone (2.5 g, 13.01 mmol) and 1M S-methyl CBS oxazaborolidine catalyst (1.3 mL, 1.3 mmol) was added freshly distilled catecholborane (1.66 mL, 15.62 mmol). The reaction mixture was maintained at −78° C. for 16 h at which time 4N HCl (5 mL in dioxane) was added and the reaction mixture was allowed to warm to room temperature. The reaction mixture was diluted with ethyl acetate and washed with a saturated brine solution. The organic layer was dried over magnesium sulfate, filtered and concentrated to provide a solid. The solid was suspended in hexanes and filtered off. The hexanes filtrate containing the desired product was concentrated and the residue subjected to flash chromatography (hexanes:ethylacetate 1:10) to provide the title compound as a colorless oil (2.2 g, 87% yield). The ratio of enantiomers was determined to be 95:5 by chiral HPLC (Chiralcel OD column, 95 hexanes:5 isopropanol mobile phase. Ret. time of the major product was 6.757 min. Ret. Time for the minor isomer was 8.274 min.).

1. additionwas added
2. washwashed with a saturated brine solution
3. dry with materialThe organic layer was dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customto provide a solid
7. filtrationfiltered off
8. additionThe hexanes filtrate containing the desired product
9. concentrationwas concentrated

ORD record

ord-4774ff80dd6047e8b3d2e3dba3046aa8

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893093B2