2,4-Dichloro-1-iodobenzene → [1-(2,4-Dichlorophenyl)piperidin-4-yl]methanol

Participants

Reaction Conditions

Reaction Steps

**_Procedure:_** To a flask was added 1,3-Dichloro-4-iodobenzene (5.89 mL, 43.41 mmol), piperidin-4-ylmethanol (5 g, 43.41 mmol), cesium carbonate (28.3 g, 86.83 mmol), 18-Crown-6 (1.377 g, 5.21 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.811 g, 1.30 mmol), and toluene (50 mL). The mixture was stirred under nitrogen and Tris(dibenzylideneacetone)dipalladium(0) (0.398 g, 0.43 mmol) was added in one portion. The resultant yellow mixture was heated with oil bath temperature set at 125°C for 3 hours. LCMS shows desired product as well as other impurities. The reaction was cooled to room temperature. Ethyl acetate (2 x 200 mL) was added and the resultant mixture was extracted with saturated aqueous sodium chloride (200 mL). The organics were collected and dried over sodium sulfate. The crude was placed in the freezer for several days. The crude was dissolved in 10% methanol:dichloromethane (200 mL) and preabsorbed onto silica gel. Column chromatography was performed on silica gel eluting with hexanes up to ethyl acetate:hexanes (10%, 20%, 40%). Desired product eluted at 40% ethyl acetate:hexanes. Collected clean fractions and concentrated to give EN01972-57-1 (2.83 g, 25.06% yield) as an orange oil. Put aside product due to shift in priorities of project.

Provenance & Evidence