2-Methoxyethanol → 6-Amino-4-(2-methoxyethoxy)nicotinonitrile

Participants

Reaction Steps

A solution of KHMDS in THF (1 M, 48.1 ml, 48.1 mmol) was added to a solution of 2-methoxy ethanol (1.68 g, 21.88 mmol) in THF (90 ml) at room temperature. After 2 minutes 6-amino-4-fluoronicotinonitrile (intermediate 21, 3.00 g, 21.9 mmol) was added and the reaction mixture stirred for 16 h at room temperature. The reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc, extracted with EtOAc (2×), the combined EtOAc layers were washed with brine, dried over MgSO4 and evaporated. The residue was triturated with EtOAc and the title compound obtained by filtration as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 6.91 (s, br, 2H), 6.03 (s, 1H), 4.19-4.13 (m, 2H), 3.34-3.28 (m, 2H), 2.51 (s, 3H).

Provenance & Evidence