3-(Benzyloxy)-5-chloro-2-iodopyrazine synthesis

Yield:1410164-82-7 50%

Reaction Conditions:

Stage #1: 2-amino-5-chloro-3-benzyloxypyrazinewith hydrogen iodide in water;acetonitrile at 0; for 0.166667 h;Inert atmosphere;
Stage #2: with sodium nitrite in water;acetonitrile at 0 - 50; for 21.1667 h;Inert atmosphere;

Steps:

7 3-(Benzyloxy)-5-chloro-2-iodopyrazine 12

A solution of 11 (0.300 g, 1.27 mmol) in acetonitrile (2.5 mL), water (3.9 mL) and 47% aqueous hydroiodic acid (3.40 mL, 19.1 mmol) was stirred at 0 °C for 10 min. A solution of sodium nitrite (1.56 g, 22.6 mmol) in water (2.6 mL) was added dropwise to the reaction mixture, which was stirred at 0 °C for a further 10 min, then heated at 50 °C for 21 h. The cooled solution was basified with 20% aqueous sodium hydroxide (11 mL). The mixture was extracted with diethyl ether (3*50 mL) and the organic layer was washed with saturated aqueous sodium metabisulfite (50 mL) and brine (50 mL), dried, filtered and concentrated. Flash column chromatography on silica, eluting with 1:1 dichloromethane/hexanes, gave 12 (0.222 g, 50%) as a pale yellow solid. Mp 265-268 °C; R_f (50% CH₂Cl₂/hexanes) 0.55; ν_max (thin film/cm^-1) 3019 (Ar CH), 1014 (C-O); (found: C, 37.55; H, 2.21; N, 7.76; C₁₁H₈N₂O₁Cl: 0.25(H₂O) requires C, 37.64; H, 2.44; N, 7.98%); δ_H (500 MHz; CDCl₃) 5.38 (2H, s, OCH₂), 7.24-7.38 (3H, m, ArH), 7.43 (2H, d, J 7.0 Hz, ArH), 7.93 (1H, s, 6-H); δ_C (125 MHz; CDCl₃) 70.0, 126.9, 128.2, 128.5, 128.7, 134.9, 135.1, 144.2, 156.0; LC-MS (3.5 min) m/z 349, 347 (MH⁺); HPLC t_R 2.95 min; purity 99%; HRMS (found: MH⁺ m/z 346.9446; requires 346.9443).

References:

Caldwell, John J.;Veillard, Nicolas;Collins, Ian [Tetrahedron,2012,vol. 68,# 47,p. 9713 - 9728,16] Caldwell, John J.;Veillard, Nicolas;Collins, Ian [Tetrahedron,2012,vol. 68,# 47,p. 9713 - 9728]