5-Iodo-2-Methoxy-nicotinonitrile synthesis

Yield:1446002-31-8 63%

Reaction Conditions:

with N-iodo-succinimide;trifluoroacetic acid;trifluoroacetic anhydride at 90; for 18 h;

Steps:

Y.a a) 5-Iodo-2-methoxy-nicotinonitrile

a)
5-Iodo-2-methoxy-nicotinonitrile
A mixture of 2-methoxy-nicotinonitrile (CAS registry 7254-34-4) (10 g, 74.6 mmol) and N-iodosuccinimide (CAS registry 516-12-1) (25.2 g, 112 mmol) was treated with trifluoroacetic acid (CAS registry 76-05-1) (68.9 ml, 895 mmol) and trifluoroacetic anhydride (CAS registry 407-25-0) (31.6 ml, 224 mmol) and the reaction mixture was heated at 90° C. for 18 h then cooled to rt and poured onto ice.
The mixture was slowly basified using 30% aq. NaOH soln., diluted with water and extracted with EtOAc.
The organic layer was successively washed with 20% aq. sodium thiosulfate soln., and sat. aq. NaHCO₃ soln., dried over Na₂SO₄, filtered and concentrated.
The title compound was obtained after flash chromatography on silica gel (cyclohexane/EtOAc, 100:0 to 20:80) as a solid (12.2 g, 63% yield)
UPLC Rt_M14=1.30 min; ESIMS: 261 [(M+H)⁺].
¹H NMR (400 MHz, CDCl₃): δ 8.54 (d, 1H), 8.11 (d, 1H), 4.06 (s, 3H).

References:

US2013/165436,2013,A1 Location in patent:Paragraph 0699; 0700; 0701