反应详情

温度

150 °C

A mixture of tert-butyl 8-bromo-2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (1.67 g, 3.7 mmol) and dicyanozinc (234.9 μL, 3.7 mmol) in DMF (10 mL) was purged with N2 for 5 min. Pd(PPh3)4 (427.6 mg, 0.37 mmol) was added. The mixture was heated in a sealed microwave vial at 150° C. overnight. The mixture was partitioned between ethyl acetate and water. The layers were separated. The aqueous layer was extracted with ethyl acetate (3×). All organic layers were combined, washed with water (3×), brine, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (10-20% EtOAc/hexanes) to provide tert-butyl 8-cyano-2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (510 mg, 35%) as a white solid. ESI-MS m/z calc. 398.2, found 399.3 (M+1)+; Retention time: 1.56 minutes (3 minute run).

1. customwas purged with N2 for 5 min
2. customThe mixture was partitioned between ethyl acetate and water
3. customThe layers were separated
4. extractionThe aqueous layer was extracted with ethyl acetate (3×)
5. washwashed with water (3×), brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness
9. customThe crude material was purified by column chromatography (10-20% EtOAc/hexanes)