2-Amino-6-methylpyridine → 2-Amino-5-chloro-6-methylpyridine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-amino-6-methylpyridine (10.80 g, 100.0 mmol) in dry DMF (50 mL) was added dropwise a solution of NCS (13.35 g, 100.0 mmol) in dry DMF (60 mL) at 0° C. over 20 min. The resulting brown yellow solution was stirred at 0° C. for 1 h, and at room temperature for 3 h, then poured into ice-water (about 300 mL). The resulting mixture was extracted with EtOAc (4×100 mL). The extracts were combined, washed with brine (6×50 mL), dried (MgSO4), and rota-evaporated. To the residual viscous black oil was added hexane (200 mL) and it was heated to boiling with stirring. The hot hexane solution was decanted carefully, concentrated to about 60 ml, then allowed to stand at room temperature overnight. The resulting crystals were filtered and dried at room temperature in vacuo, giving 6.06 g (42%) of 45 as orange-colored long needles, mp 74°-5° C. (lit. 73°-4° C., Cress et al., J. Org. Chem. 93-6 (1976)). 1H NMR (CDCl3) δ 2.439 (s, 3H), 4.376 (bs, 2H), 6.302 (d, 1H, J=8.5), 7.340 (d, 1H, J=8.5).

Provenance & Evidence