3-(BENZYLOXY)-5-BROMOPICOLINONITRILE synthesis

Yield:1393534-88-7 87.3%

Reaction Conditions:

Stage #1: benzyl alcoholwith sodium hydride in tetrahydrofuran at 0 - 35; for 1.5 h;Inert atmosphere;
Stage #2: 5-bromo-3-nitropyridine-2-carbonitrile in tetrahydrofuran at 20; for 24 h;Inert atmosphere;Temperature;

Steps:

3-(Benzyloxy)-5-bromopicolinonitrile (6).

A mixture of THF (1.8L) and benzyl alcohol (59mL, 114mmol) was cooled to 0°C. NaH was added slowly to the mixture at 0°C. After addition, the mixture was stirred at room temperature for 1h and 35°C for another 0.5h. The resultant solution was added to the solution of 5-bromo-3-nitropicolinonitrile (5, 100g, 438mmol) in THF (1.3L) and the mixture was stirred at room temperature for 24h. The reaction mixture was quenched with H₂O (200mL). After quenched, the mixture was concentrated to a volume of about 200mL. Dichloromethane (1.5L) was added, and the higher aqueous phase was removed. The organic phase was wash with saturated aqueous NaHCO₃ (1.0L×1), water (1.0L×3), saturated aqueous NaCl (1.0L×1). The organic phase was concentrated, and dried under vacuum at 55°C to give 6 (110.0g, 87.3% yield, 99.5% purity by HPLC) as a brown solid.

References:

Lei, Yonghua;Hu, Tianhan;Hu, Mingyang;Yang, Li;Wu, Yue;Xiang, Hua;Zhang, Lianshan;Shen, Lingjia;You, Qidong;Zhang, Xiaojin [Tetrahedron Letters,2015,vol. 56,# 35,art. no. 46502,p. 5017 - 5019]