Tetrahydrofuran → (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzyl]-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one

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Reaction Steps

To a solution of the product from Example 201C (64 mg, 0.233 mmol) in 4:1 tetrahydrofuran:N,N-dimethylformamide (2 mL) was added sodium hydride (11.2 mg, 0.280 mmol). The resulting mixture was stirred at ambient temperate for 30 minutes, and 1-(bromomethyl)-3-(trifluoromethyl)benzene (42.8 μL, 0.280 mmol) was added. The mixture was stirred at ambient temperature for 1 hour and was then partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography on a 12 g silica gel column eluting with 5% ethyl acetate/hexanes for 3 minutes then a gradient to 100% ethyl acetate over 20 minutes. The title compound was obtained as a thick oil (13 mg, 13%). 1H NMR (300 MHz, methanol-d4) δ ppm 7.99 (dt, J=11.3, 5.7 Hz, 2H), 7.65-7.49 (m, 4H), 5.42 (dd, J=12.6, 5.1 Hz, 1H), 4.70 (d, J=3.7 Hz, 2H), 3.81-3.61 (m, 2H), 3.50-3.35 (m, 1H), 3.16 (dd, J=13.4, 8.3 Hz, 2H), 2.87 (qd, J=10.1, 4.9 Hz, 1H), 2.39 (dd, J=10.4, 5.0 Hz, 1H), 2.20-1.85 (m, 3H), 1.02-0.82 (m, 4H); MS (ESI) m/z 275 (M+H)+.

Provenance & Evidence