Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → Benzamide

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Reaction Steps

To a solution of 2-[4-benzo[b]thiophene-2-sulfonylamino]benzoic acid (300 mg, 0.90 mmol) in DMF (20 mL) at room temperature were added 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 207 mg, 1.08 mmol), and 1-Hydroxybenzotriazole hydrate (HOBT, 182 mg, 1.35 mmol). The mixture was stirred 20 min. at room temperature then NH2OTHP (158 mg, 1.35 mmol) was added. The resulting mixture was heated at 50° C. for 24 h then stirred at room temperature for 24 h. The DMF solvent was evaporated under reduced pressure and the residue was dissolved in CH2Cl2 and washed with brine or a saturated aqueous solution of NaHCO3. The combined organic extracts were dried over (MgSO4) then condensed. The crude compound was purified by flash chromatography using CH2Cl2/MeOH (9:1) as solvent mixture. The residue was then dissolved in methanol (20 mL) then 10-camphorsulfonic acid (CSA, 100 mg, 0.45 mmol) was added. The mixture was stirred 2 h at room temperature then the solvents were evaporated under reduced pressure at room temperature to avoid thermal decomposition. The crude was purified by flash chromatography using CH2Cl2/MeOH (9:1) as solvent mixture. A second purification was performed using a preparative high pressure liquid chromatography using a gradient of water/CH3CN (10-85%) as solvent giving the title compound 13 as a red solid (212 mg, 68%).

Provenance & Evidence