Sulfuric Acid → 5-[[(2,2-Dimethyl-1-oxopropyl)amino]methyl]-2-methylbenzoic acid

Participants

Reaction Steps

Cool sulfuric acid (3.67 mL) to 0° C., and add 2-methylbenzoic acid (500 mg, 3.67 mmol, 1.0 equiv) and N-(hydroxymethyl)-2,2-dimethylpropanamide (506 mg, 3.86 mmol, 1.05 equiv). Allow the mixture to warm to room temperature, and stir overnight. Dilute with water (25 mL) and extract with EtOAc (50 mL). Dry the organic layer over MgSO4, filter, and concentrate under reduced pressure to give the crude compound. Purify the material by reverse-phase HPLC on an XBridge Prep C18 5 μM OBD 30×75 mm column, eluting with a gradient of 5-50% (0.1% TFA in acetonitrile) in (0.1% TFA in water) to give the title compound (255 mg, 28%). 1H NMR (DMSO-d6, 400 MHz): δ 12.76 (s, 1H), 8.09 (t, 1H, J=6.0 Hz), 7.67 (d, 1H, J=1.6 Hz), 7.25 (dd, 1H, J=8.0, 1.6 Hz), 7.21 (d, 1H, J=8.0 Hz), 4.22 (d, 2H, J=6.0 Hz), 2.46 (s, 3H), 1.10 (s, 9H).

Provenance & Evidence