2-(4-Fluorophenyl)acetic acid → 1-[(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-(4-fluorophenyl)ethanone

Participants

Reaction Steps

To a mixture of the product from Example 54F (30 mg, 0.115 mmol) and 2-(4-fluorophenyl)acetic acid (21.3 mg, 0.138 mmol) was added a solution of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (33.1 mg, 0.173 mmol) in dichloromethane (1.0 mL). To the resulting solution was added hydroxybenzotriazole hydrate (26.5 mg, 0.173 mmol) and diisopropylethylamine (0.040 mL, 0.230 mmol), and the mixture was stirred at room temperature for 16 hours. The mixture was partitioned between water and ethyl acetate, and the organic extract was dried over Na2SO4. The mixture was filtered and concentrated in vacuo, and the crude product was purified by column chromatography on silica gel using a solvent gradient of 0-100% ethyl acetate in hexanes. The title compound was obtained as a colorless solid (16 mg, 35%). 1H NMR (300 MHz, CDCl3) δ ppm 0.85-1.03 (m, 4 H), 1.78-2.06 (m, 3 H), 2.11-2.48 (m, 3 H), 2.63-3.27 (m, 3 H), 3.61-4.00 (m, 4 H), 4.55-4.85 (m, 1 H), 5.25-5.40 (m, 1 H), 6.96-7.06 (m, 2 H), 7.15-7.25 (m, 2 H), 7.93 (d, J=1.36 Hz, 1 H), 8.01 (d, J=1.36 Hz, 1 H); MS (ESI) m/z 397 (M+H)+.

Provenance & Evidence