Hydrochloric Acid → 2-fluoro-beta(R)-(hydroxymethyl)benzenepropionitrile

Temperature

0 °C

3-[(R)-β-Cyano-α-(2-fluorophenyl)-propionyl]-4-(R)-phenyl-2-oxazolidinone (400 g, 1.18 mol) is suspended in THF (4000 mL) and H2O (25 mL). The reaction mixture is cooled in ice bath to 0° C. and a solution of LiBH4 in THF (2M, 887 ml, 1.77 mol, 1.5 eq) is added slowly. The mixture is then stirred at 0° C. for 2 hours, after which 2N HCl (1500 mL) is cautiously added. The resulting solution is then extracted with Et2O (2×1500 mL). The combined organic phases are then washed with saturated NaCl solution (2×1500 mL), dried over MgSO4 and concentrated in vacuo. The solid 4(R)-phenyl-2-oxazolidinone is recovered by filtration and washed with Et2O (2×100 mL). The filtrate is then chromatographed (silica gel, EtOAc/Hexanes, 1:3 ) to give β(R)-(hydroxymethyl)-β-(2-fluorophenyl)-propionitrile as an oil.

1. extractionThe resulting solution is then extracted with Et2O (2×1500 mL)
2. washThe combined organic phases are then washed with saturated NaCl solution (2×1500 mL)
3. dry with materialdried over MgSO4
4. concentrationconcentrated in vacuo
5. filtrationThe solid 4(R)-phenyl-2-oxazolidinone is recovered by filtration
6. washwashed with Et2O (2×100 mL)
7. customThe filtrate is then chromatographed (silica gel, EtOAc/Hexanes, 1:3 )

ORD record

ord-40ad83eb847c45d1b7bcd2e85099a6c7

Source dataset

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06043365