Nicotinic Acid → HCID 21981146, compound

Participants

Reaction Steps

Oxalyl chloride (2.8 mL, 32 mmol) is added to a suspension of nicotinic acid (3.7 g, 30 mmol) in methylene chloride (35 ml) followed by 2 drops of DMF. The reaction is refluxed for 1.5 h and all the volatiles are removed on a rotovap. Alternatively, rather than convert nicotinic acid to the acid chloride, commercially available nicotinyl chloride hydrochloride may be used. The solid is resuspended in methylene chloride/acetone (1:1) (50 ml) and an acetone (10 ml) solution of ammonium thiocyanate (3.5 g, 45 mmol) is added. The reaction is stirred for 1 h at room temperature followed by the addition of 3-phenoxy aniline. The stirring is continued over night at room temperature. The solvent is evaporated and the residue suspended in water (100 ml) and extracted with methylene chloride (3×75 ml). The organic layers are combined, dried over sodium sulphate, filtered to remove any insoluble materials and evaporated. The residue is purified by column chromatography on silica gel and crystallized from methanol to give the desired product. MP: 144.5-145.5° C., 1H NMR (300 MHz, DMSO): δ 12.330 (s, 1H), 11.93 (s, 1H), 9.07 (s, 1H), 8.80 (m, 1H), 8.300 (d, 2H, J=8.1 Hz), 7.955 (s, 1H), 7.81 (d, 1H, J=9.0 Hz), 7.57 (m, 1H), 7.299 (d, 1H, J=9.0 Hz), 4.13 (t, 2H, J=6.2 Hz), 1.77-1.72 (m, 2H,), 1.44-1.34 (m, 4H), 0.92-0.87 (t, 3H, J=7.1). MS (APCI) m/z 350.1 [M+H]+.

Provenance & Evidence