Cesium carbonate → HCID 69420920, compound

Participants

Reaction Conditions

Reaction Steps

An intermediate compound 1-(3-Chloro-2-methoxy-phenyl)-piperazine, was produced as follows. A solution of 2,6-dichloroanisole (1.55 mL, 11.30 mmol) in dry toluene (40 mL) was degassed for 10 min by blowing nitrogen into the solution. This solution was then added via cannula to a flask containing Boc-piperazine 3.16 g, 16.90 mmol), Cs2CO3 (5.15 g, 15.80 mmol), Pd2(dba)3 (414 mg, 0.452 mmol, 4 mol %) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (356 mg, 0.904 mmol, 8 mol %) under nitrogen. The reaction mixture was heated at 100° C. overnight (16 h). MS showed a small product peak and a large Boc-piperazine peak. TLC (10% EtOAc/Hex) showed a product spot. The reaction was allowed to cool to room temperature and Et2O was added. The mixture was filtered through Celite washing with Et2O. The filtrate was washed 3 times with 0.5 M citric acid (to remove excess Boc-piperazine) and once with brine, dried over MgSO4 and concentrated to give a brown oil. Purification by SiO2 chromatography (10% EtOAC/Hexanes) gave 4-(3-chloro-2-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester as a pale yellow solid (278 mg, 8%).

Provenance & Evidence