Electric Literature of 136618-42-3, These common heterocyclic compound, 136618-42-3, name is Benzyl 4-iodobenzoate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a solution of the 6-methyl-1 H-indazol-4-amine (8.26g, 54.2mmol) in dry DMF (100ml) was added iodobenzoic acid benzyl ester (19g, 56.2mmol) followed by potassium carbonate (8.15g, 59mmol), 1 /?,2/?-lambda/,lambda/’-dimethyl-1 ,2-cyclohexanediamine (0.425g, 3.0mmol) and copper (I) iodide (0.284g, 1.5mmol). The mixture was heated to 11 O0C for 5hr when LCMS showed ca. 50% conversion. Potassium carbonate (8.15g, 59mmol) was added followed by copper (I) iodide (0.284g, 1.5mmol) and 1 /?,2/?-lambda/,lambda/’-dimethyl-1 ,2-cyclohexanediamine (0.425g, 3.0mmol) and the mixture was heated to 1 1O0C for 5hr when LCMS showed absence of starting materials. The majority or the solvent was removed in vacuo and the residue was partitioned between ethyl acetate (500ml) and water (500ml). The emulsion which ensued was filtered through celite and separated. The organics were washed with saturated sodium thiosulphate solution (250ml) then brine (250ml) and dried (sodium sulphate). The mixture was filtered and concentrated in vacuo. The residue (ca. 22g) was dissolved in DCM (100ml), placed on a silica (50Og) column, pre-eluted with cyclohexane and eluted with DCM (500ml), 2% ethyl acetate/DCM (1000ml), 3% ethyl acetate/DCM (2000ml), 4% ethyl acetate/DCM (1000ml), 5% ethyl acetate/DCM (2000ml) then 10% ethyl acetate/DCM (1000ml) to give the title compound as a pale yellow solid (5.6g, 27.9%). LCMS: tRET = 3.72min, MH+ 358.1H NMR (400 MHz, CHLOROFORM-d) deltappm 8.24 (d, 2H) 8.1 1 (s, 1 H) 7.85 (d, 2H) 7.49 (d, 2H) 7.35 – 7.45 (m, 3H) 7.00 (s, 1 H) 6.32 (s, 1 H) 5.41 (s, 2H) 2.40 (s, 3H).The impure fractions (10g) were purified by CombiFlash Companion XL using a RediSep cartridge (75Og silica) eluting with a gradient of DCM/20% ethyl acetate/DCM over eight column volumes. This gave additional product (1.5g, 7.47%).
Statistics shows that Benzyl 4-iodobenzoate is playing an increasingly important role. we look forward to future research findings about 136618-42-3.