Potassium Carbonate → (R)-2-Chloro-3-(2-methylpiperazin-1-YL)pyrazine

Participants

Reaction Conditions

Reaction Steps

A mixture of the product obtained in Step 1 above, 2,3-dichloropyrazine (154 g, 1.00 mmol) and K2CO3 (160 g, 1.20 mol) in DMF (1 L) was heated at 110° C. for 20 h with vigorous stirring. (TLC monitoring system: CHCl3: EtOH (20:1); silica). The mixture was cooled and poured slowly into water (6 L) with stirring. The solid was collected, washed with water, dried, dissolved in CHCl3 (1 L), diluted with n-heptane (1 L), and filtered through SiO2. Solvents were evaporated off. The resulting oil was dried under vacuum (3 mm/50° C., 30 min) to remove the DMF. The oil was dissolved in hot ethanol (1 L.), and HCl (10% aqueous solution, 300 mL) was added slowly. Trityl carbinol began to crystallize out after 10 min. After 30 min, the formed trityl carbinol was filtered off and the ethanol was evaporated. The aqueous solution was extracted by ether (2×200 mL) and made basic by addition of K2CO3 to pH 12. The alkaline layer was extracted with CHCl3 (3×200 mL). The combined organic layers were dried (K2CO3) and concentrated to give 140 g (66%) of the title compound.

Provenance & Evidence