Sodium hydride → (7S,8aS)-7-(4-Fluorobenzyl)oxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

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Reaction Steps

A solution of 0.23 g (0.91 mmol) of (7S,8aS)-7-hydroxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 18) in 10 mL of dry THF was treated with 40 mg (1.0 mmol) of sodium hydride (60% oil dispersion), followed by 0.125 mL (1.0 mmol) of 4-fluorobenzyl bromide and 17 mg (0.05 mmol) of tetra-n-butylammonium iodide. The mixture was stirred at ambient temperature for 16 h, and warmed to 50° C. for 4 h. The suspension was cooled, the solvent was evaporated, and the residue partitioned between ethyl acetate and water. The layers were separated, and the organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 95:5 chloroform: methanol gave 0.135 g (41%) of the title compound. mp (.HCl) 165°-168° C. HRMS calcd for C19H22ClFN3O (MH+): 362.1435, found: 362.1451.

Provenance & Evidence