Tetrahydrofuran → 2-(3,4-Dichloro-phenyl)-5-(tetrahydro-pyran-4-yloxy)-pentanenitrile

Participants

Reaction Steps

To a suspension of NaH (7.6 g, 0.191 mol) in THF (90 mL) was added slowly a solution of 3,4-dichloro-phenylacetonitrile phenylacetonitrile (32.3 g, 0.174 mol) in dry THF (40 mL). The mixture was stirred at room temperature for 2 hours, then cooled in dry ice-acetone bath. A solution of THP protected 3-bromopropanol (42.6 g, 0.191 mol, 1.1 eq) in dry THF (50 mL) was added dropwise to this solution. After the addition was completed, the reaction was warmed to room temperature and stirred at room temperature overnight (20 hours). The reaction was then quenched with saturated NH4Cl solution (ca. 5 mL) and ether (300 mL) was added. The organic phase was then washed with saturated NaHCO3, brine, and dried (MgSO4). After filtration, solvent was removed, and the crude oil was purified by flash column chromatography (Hexane-AceOEt/8:1). The product weight 46.8 g (82.2%) as light yellow oil.

Provenance & Evidence