Phthalimide → (3-Chloropyrazin-2-yl)methanamine dihydrochloride

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Reaction Steps

To a solution of (3-chloropyrazin-2-yl)methanol (B. Klein et al. J. Org. Chem. 1963, 28, 1682.) (10.78 g, 74.6 mmol), phthalimide (13.18 g, 89.7 mmol) and triphenylphosphine (23.78 g, 90.8 mmol) in THF (350 mL) was added DIAD (17.8 mL, 90.8 mmol) and the mixture stirred at ambient temp for 16 h. The mixture was concentrated by rotary evaporation. The intermediate 2-((3-chloropyrazin-2-yl)methyl)isoindoline-1,3-dione was taken up in CH2Cl2 (300 mL) and methanol (450 mL) and treated with anhydrous hydrazine (6.0 mL, 190 mmol) at ambient temperature for 18 h. The mixture was filtered and the precipitate discarded. The filtrate was concentrated by rotary evaporation, then taken up in EtOAc and refiltered. The filtrate was concentrated to dryness, dissolved in 600 mL EtOAc, then treated with 40 mL of 4N HCL in dioxane. The precipitated solids were collected, washed with ether and vacuum dried to give 12.53 g tan solid.

Provenance & Evidence