p-Toluenesulfonic acid monohydrate → HCID 17968162, compound

Participants

Reaction Steps

p-Toluenesulfonic acid monohydrate (45.2 mmol) is added to 4-{2-fluoro-4-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-piperazine-1-carboxylic acid, tert.-butyl ester (22.6 mmol) in MeOH (50 ml) at room temperature. The reaction mixture is stirred at room temperature for 1.5 h. After the mixture is extracted with AcOEt, the organic layer is washed with brine, dried over magnesium sulfate and filtered. The solvent is evaporated. To the residue in CH2Cl2 (9 ml), TFA (17.5 ml) is added at 0° C. The reaction mixture is stirred at room temperature for 1 h. The solvent is removed by evaporation and dried to give brown crude oily product, 2-(3-fluoro-4-piperazin-1-yl-phenoxy)-ethanol. To the crude product in DMF (100 ml), potassium carbonate (113 mmol) is successively added at 0° C. The mixture is stirred at 0° C. for 15 min. 6-Bromomethyl-7-(2,2-dimethyl-propyl)-7.H.-pyrrolo[2,3-.d.]pyrimidine-2-carbonitrile (22.6 mmol) is added to the mixture at 0° C. The reaction mixture is stirred at room temperature for 3 h and quenched with saturated ammonium chloride. The mixture is extracted with AcOEt. The combined extracts are washed with H2O, brine and dried over magnesium sulfate. The solvent is evaporated and the residue is purified by column chromatography on silica gel using n-hexane:AcOEt=3:2 (v/v).

Provenance & Evidence