Hydrogen Peroxide → HCID 67403888, compound

Participants

Reaction Conditions

Reaction Steps

To a pressure vessel were added the above methyl 4-cyano-2-fluoro-5-iodobenzoate (˜0.93 mmol), cesium carbonate (606 mg, 1.86 mmol), pentan-3-amine (325 uL, 2.79 mmol), XANTPHOS (54 mg, 0.093 mmol), tris(dibenzylideneacetone)dipalladium(0) (43 mg, 0.047 mmol), and dioxane (4 mL). The vessel was sealed and heated to 95° C. for ˜17 h. After cooling to room temperature, the mixture was filtered through celite, and the filter cake rinsed with ethyl acetate. The filtrate was then concentrated. The residue was subject to column chromatography (10% ethyl acetate in hexanes). Eluent containing the desired project was collected and concentrated to afford an impure residue. This residue was dissolved in DMSO (6 mL) and was treated with potassium carbonate (111 mg, 0.8 mmol) and 30% aqueous hydrogen peroxide (150 uL). After stirring at room temperature for 30 min, the mixture was diluted with ethyl acetate. The organic solution was washed with a mixture of water and 10% aqueous lithium chloride. The aqueous wash was extracted with ethyl acetate. The combined organic extracts were washed with 10% aqueous lithium chloride, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by gradient column chromatography (30% ethyl acetate in hexanes to 50% ethyl acetate in hexanes) to provide methyl 4-(aminocarbonyl)-2-fluoro-5-(pentan-3-ylamino)benzoate (73.7 mg, 0.26 mmol, 28% yield). 1H NMR (400 MHz, CDCl3): 7.42 (d, 1H), 7.18-7.15 (m, 2H), 5.86 (br s, 2H), 3.94 (s, 3H), 3.37-3.29 (m, 1H), 1.67-1.47 (m, 4H), 0.93 (t, 6H).

Provenance & Evidence