Bromoacetonitrile → HCID 117992809, compound

Participants

Reaction Steps

The following reaction was repeated twice and combined to provide the yield below. To a −78° C. solution of crude ethyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate (69 g, 0.28 mol) in dry THF (1.0 L) was added lithium bis(trimethylsilyl)amide/THF (1.0 M, 400 mL, 0.40 mol) dropwise and stirred for 40 min. A solution of 2-bromoacetonitrile (54.5 g, 0.45 mol) in THF (70 mL) was then added dropwise over 1 h at −70° C. The reaction was then warmed to r.t. and stirred overnight. The reaction was quenched with saturated aqueous NH4CI and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated. Purification by silica gel column chromatography (2-8% EtOAc/PE) provided ethyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate (100 g, 62%) as an oil which solidified over several days. 1H NMR (600 MHz, CDCl3) δ 1.19 (t, 3H), 1.76 (s, 3H), 3.13 (q, 2H), 3.96 (s, 3H), 4.14-4.24 (m, 2H), 7.02 (d, 1H), 7.60 (d, 1H).

Provenance & Evidence