2-Bromo-4-iodo-5-cyanopyridine 25.320g (81.97mmol) solid in a 2L round flask with a large egg-shaped stirbar was flushed with Ar and anhydrous toluene 1L was added via canula. The mixture was stirred and gently heated until complete dissolution, then cooled to 0C. With vigorous stirring on ice bath, diisobutylaluminum hydride solution 1M in hexane, 83mL was added by syringe, dropwise over a 20 min period. The mixture was stirred at 0C for additional 90 min, then cooled down to -78C. Ice-cooled mixture of 2M aqueous sulfuric acid 170mL and THF 350mL was gradually added into the reaction mix with vigorous stirring, the cooling bath was then removed and the mixture was let stirring in open flask (gas evolution) at ambient temperature overnight (15 hours). The next day water 400mL was added and the mixture was stirred for additional 30 min and separated. The organic phase was washed with water 500mL and saturated bicarbonate 500mL. The aqueous phases were re-extracted with ethyl acetate 500mL. The combined organic extracts were dried with MgSO4 and concentrated on rotovap down to aprox 300mL total volume from a 30C bath and cooled to RT. The precipitated product (13.398g, 98% pure, a cream-colored fluffy fibrous crystals) was collected by filtration, washed with toluene (4x20mL) and hexane and dried on highvac. The filtrates were evaporated to dryness. The residue was re-crystallized from acetonitrile 80mL (dissolved at reflux, 2h at RT, then at 0C overnight) filtered, rinsed with chilled acetonitrile and dried, to provide the second crop of product 7.814g (95% pure) as a tan crystalline solid. The combined yield was 21.212g (83% th).
1H(d6-DMSO, 400MHz): 9.950(s, 1H), 8.573(s, 1H), 8.434(s, 1H); 13C(d6-DMSO, 100MHz): 193.46, 151.48, 146.35, 138.54, 130.74, 112.97
The nitrile preparation was described here on July 1, 2008