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Markevitch et al.
mixture was purged with N2 (g) and cooled to ꢁ78ꢀC. A solution
of n-BuLi (6.5 mmol) in hexanes was added dropwise, and the mixture
was stirred at this temperature for 2 h. A solution of t-butyl isocyanate
(850 mL, 7.2 mmol) in 2.5 mL of toluene was added dropwise, and the
reaction mixture was stirred for 1 h. The mixture was allowed to warm
to ꢁ10ꢀC, and was quenched with aqueous NH4Cl (130 mL) and stirred
for 30 min. The layers were separated and the toluene layer was dried
over Na2SO4, filtered, and concentrated to dryness to furnish 1.4 g (99%)
1
of crude 6, which was judged to be 90–95% pure by H NMR: 1H NMR
(300 MHz, CD3OD): ꢀ 8.66 (d, 1H, J ¼ 1.2), 8.12 (d, 1H, J ¼ 6.3), 7.94
(d, 1H, J ¼ 6.3), 1.44 (s, 9H).
5-Bromopyridine-2-carbonitrile (1). Crude 6 (1.4 g) was dissolved in a
mixture of toluene (5 mL) and POCl3 (5 mL). The resulting solution was
stirred at 110ꢀC for 5 h. The reaction was cooled to room temperature
and poured into a flask containing ice cold H2O (80 mL). The pH of the
resulting solution was adjusted to ꢂ12 by the slow addition of aqueous
2 N NaOH. The product was extracted from the aqueous layer using
EtOAc (50 mL Â 2). The organic layers were collected, dried over
Na2SO4, and concentrated to dryness. Compound 1 (734 mg, 75% two
1
step yield) was estimated to be 95% pure by H NMR and was subse-
quently used in additional reactions without further purification. A small
sample was recrystallized from hexanes to afford the analytical sample:
Rf ¼ 0.50 (hexanes:EtOAc ¼ 4:1 v/v). 1H NMR (300 MHz, CDCl3): ꢀ 8.79
(d, 1H, J ¼ 2.1), 7.99 (d, 1H, J ¼ 2.1, 8.4), 7.59 (d, 1H, J ¼ 8.4). IR (NaCl,
neat, cmꢁ1): 2232. LC-MS: M þ CH3CN 224, retention time 2.22 min,
purity 98.4% (method: Phenomenex Synergi 4 m Hydro-RP column;
2 mL/min flow rate, 5ꢁ100% CH3CN gradient in 0.1% formic acid).
M.p.: 128–129ꢀC (Lit. m.p. 100–110ꢀC, 3 mmHg).
ACKNOWLEDGMENTS
The authors thank William J. Watkins and Constantine G. Boojamra
for reviewing the manuscript.
REFERENCES
1. Sakamoto, T.; Keneda, S.; Nishimura, S.; Yamanaka, H. Site-
selectivity in the cyanation of 3-substituted pyridine 1-oxides with
trimethylsilanecarbonitrile. Chem. Pharm. Bull. 1985, 33 (2),
565–571.