Ethanol → HCID 67432793, compound

Participants

Reaction Steps

DCC (5.24 g, 25.4 mmol) was added in portions over 10 min to a solution of 4-chloronicotinic acid (2.00 g, 12.7 mmol), ethanol (1.75 g, 38.1 mmol) and DMAP (0.19 g, 1.52 mmol) in DMF (20 mL) at 0° C. After stiffing for 1 h the reaction mixture was allowed to warm to room temperature and stirred overnight. Water (100 mL) was added and the solid formed was filtered off. The filtrate was extracted with DCM, washed with water, dried (MgSO4) and the solvent was removed in vacuo. The crude ethyl 4-chloronicotinate (5.8 g) was dissolved in DMF (15 mL). Phenol (2.86 g, 30.4 mmol), copper powder (0.48 g, 7.59 mmol), copper iodide (0.72 g, 3.80 mmol) and K2CO3 (4.20 g, 30.4 mmol) were added. The reaction mixture was heated to 80° C. for 3 h then allowed to cool to room temperature and left overnight without stirring. The mixture was poured into water and extracted with EtOAc. The combined organic layers were washed with aqueous NaOH solution (1 M), water and dried over MgSO4. Purification by flash chromatography (DCM/EtOAc, gradient 1-10% EtOAc) provided ethyl 4-phenoxynicotinate (1.59 g, 51% over 2 steps). ESI-MS [M+H]+=244.1.

Provenance & Evidence