Isopropanol → (7S,8aS)-7-(4-Fluorophenoxy)-2-(5-fluoropyrimidin-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 0.83 g (2.5 mmol) of (7S,8aS)-7-(4-fluorophenoxy)-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine in 10 mL of methanol and 1.8 mL of aqueous ammonium formate (5M) was treated with an aqueous slurry of 0.325 g of 10% palladium on carbon and the mixture was stirred at room temperature for 24 h. The mixture was filtered through Celite, evaporated, re-evaporated with another 100 mL of chloroform, dissolved in 100 mL of chloroform, dried (magnesium sulfate), filtered and evaporated. The crude amine (0.61 g, ca. 2.5 mmol), 0.50 g (3.75 mmol) of 2-chloro-5-fluoropyrimidine (Dunaiskis, A.; et al. Org. Prep. Proc. Int., 1995, 27, 600-602), 0.86 g (6.2 mmol) of potassium carbonate and 15 mL of 2-propanol were refluxed for 5.5 h. The mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate (3×). The combined organic phase was washed with water (2×) and brine (1×), dried (magnesium sulfate), filtered and evaporated. Purification by silica gel MPLC starting with 70:30 ethyl acetate:hexane and ramping to 50:50 ethyl acetate:hexane at 30 min, gave 0.30 g (36%) of the title compound. mp (.HCl) 90°-95 ° C. 13C NMR (base, CDCl3): δ 36.6, 43.6, 48.7, 60.5, 62.1, 75.6, 115.67, 115.98, 116.08, 116.18, 144.97, 145.26, 149.9, 153.2, 153.8, 155.6, 158.8. HRMS calcd for C17H19F2N4O (MH+): 333.1527, found: 333.1556.

Provenance & Evidence