2-iodo-1-methoxy-4-nitronaphthalene synthesis

Yield:1429765-70-7 70%

Reaction Conditions:

with N-iodo-succinimide;trifluoroacetic acid for 20 h;Reflux;Inert atmosphere;Temperature;Time;

Steps:

2-Iodo-l-methoxy-4-nitronaphthalene (38)

2-Iodo-l-methoxy-4-nitronaphthalene (38). A mixture of commercially available 1-methoxy-4-nitronaphthalene (2.1 g, 10.4 mmol), N-iodosuccinimide (2.7 g, 12 mmol) in TFA (40 mL) was heated to reflux and stirred for 20 h under a N₂ atmosphere. The reaction mixture was diluted with EtOAc (40 mL), washed with saturated aqueous Na₂S₂03 solution (30 mL), saturated aqueous NaHCC>3 (30 mL x 2), and brine (30 mL). The organic layer was dried (MgS0₄), filtered and silica was added to filtrate and the solvent was removed under reduced pressure. The adsorbed crude residue was purified by flash column chromatography (100% hexane) on silica gel to give 38 (2.4 g, 70%) as a light yellow solid.^]H NMR (400 MHz, CDC1₃) δ 8.59 (s, 1H), 8.58 (s, 1H), 8.21 (d, / = 8.42 Hz, 1H), 7.74 (t, 7 = 7.53 Hz, 1H), 7.65 (t, 7 = 7.53 Hz, 1H), 4.03 (s, 3H); ¹³C NMR (100 MHz, CDC1₃) δ 161.69, 142.85, 134.07, 129.99, 128.55, 128.08, 126.55, 123.92, 123.02, 83.35, 62.20; ESI MS: m/z 330.0 (M+H)⁺. Note: R_f of starting material and product are very close and a good separation is achieved with a relatively long silica gel column and 100% hexane gradient. >95% pure product is needed for pd-catalyzed coupling step.

References:

WO2013/52943,2013,A2 Location in patent:Page/Page column 109; 110