Piperazine → 6-Methoxy-5-piperazin-1-yl-quinoline

Participants

Reaction Conditions

Reaction Steps

To an oven-dried 100 mL flask under N2 atmosphere was added 5-bromo-6-methoxyquinoline (3 g, 12.6 mmol), piperazine (6.5 g. 75.6 mmol), Pd(dba)2 (570 mg, 5 mol %), P(t-Bu)3 (0.628 mL, 5 mol %) and sodium t-butoxide (1.82 g, 18.9 mmol). 50 mL dry o-xylene was added and the reaction mixture stirred and heated at 120° C. for 3 hours, then at room temperature overnight. The reaction mixture was poured into H2O (100 mL) and extracted into EtOAc (3×100 mL). The organic fractions were combined, dried over Na2SO4, concentrated and purified by column chromatography (10% MeOH/CH2Cl2+NH4OH) affording 170 mg (6%) of 6-methoxy-5-piperazin-1-yl-quinoline. This material was used without further purification (combined with another batch) in the next step. (Ref: Tet Lett. 1998, 39, p. 617-620).

Provenance & Evidence