Cesium carbonate → (1-(6-Chloro-3-pyridinyl)-4-piperidinyl)acetonitrile

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

2-Chloro-5-iodopyridine (0.278 g, 1.16 mmol), 2-(piperidin-4-yl)acetonitrile hydrochloride (253) [Vidaluc, J.-L. et al., Novel J. Med. Chem. 1994, 37, (5), 689-695] (0.186 g, 1.16 mmol), Pd2(dba)3 (0.0531 g, 0.0580 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.0671 g, 0.116 mmol) and cesium carbonate (0.945 g, 2.90 mmol) were combined in a screw cap vial and solvated under argon atmosphere with degassed dioxane (4.5 mL). The reaction was briefly sparged with argon, then sealed and stirred at 105° C. After 3 h, the reaction was poured into water (30 mL) and extracted with 10% methanol in CH2Cl2 (3×20 mL). The combined organics were dried with sodium sulfate and concentrated in vacuo. Silica gel chromatography (gradient elution 10 to 50% ethyl acetate in hexanes) afforded compound 254 (0.110 g, 40.2% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.23-1.44 (m, J=11.98, 11.98, 11.84, 3.72 Hz, 2 H) 1.68-1.90 (m, 3 H) 2.54 (d, 2 H) 2.75 (td, J=12.42, 2.15 Hz, 2 H) 3.77 (d, J=12.52 Hz, 2 H) 7.26 (d, J=9.00 Hz, 1 H) 7.42 (dd, J=8.80, 3.33 Hz, 1 H) 8.06 (d, J=3.13 Hz, 1 H) ppm.

Herkunft & Nachweise