Dimethylformamide → 8-Cyano-1,2,3,4-tetrahydronapthyridine

Participants

Reaction Steps

To a solution of 0.8914 g (4.18 mmol) 33 in 20 mL DMF was added 0.2949 g (2.51 mmol) zinc cyanide and 0.4825 g (0.42 mmol) tetrakis(triphenylphosphine)palladium(0). After 17 h at 100° C., the reaction mixture was cooled to room temperature, diluted with 120 mL toluene and washed 60 mL 2N NH40H. The aqueous layer was extracted with 60 mL toluene. The combined organic layers were washed with 60 mL brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (50×80 mm silica gel, 5% (10% NH4OH:MeOH):CH2Cl2) yielded 0.7609 g of 34 and triphenylphosphine oxide. This material was partitioned between 50 mL ethyl ether and 50 mL 1M HCl. The aqueous layer was brought to pH 12 with 50% aqueous NaOH and extracted with 3×100 mL CH2Cl2. The combined CH2Cl2 layers were washed with 100 mL brine, dried over Na2SO4, filtered and concentrated in vacuo to give 34. 1H NMR (CDCl3, 400 MHz) δ 8.276 (s, 1H, ArH); 8.037 (s, 1H, ArH); 3.487-3.452 (m, 2H, CH2); 2.729 (t, 2H, J=6.22 Hz, CH2); 2.001-1.942 (m, 2H, CH2); MS (Electrospray): n/z 159.9 (M+H).

Provenance & Evidence