1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(4-formylphenyl)acetic Acid

Participants

Reaction Steps

To a solution of 2-(3-formylphenyl)acetic acid (394 mg, 2.4 mmol) in DMF (5 mL) was added (1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethanol (1.0 g, 2.4 mmol) followed by DMAP (147 mg, 1.2 mmol) and EDC.HCl (930 mg, 4.8 mmol). The mixture was allowed to stir a room temperature for 18 hours. The solvent was removed in vacuo and the residue was partitioned between DCM (10 mL) and waturated sodium bicarbonate solution (10 mL). The organic phase was passed through a hydrophobic fit and the solvent was removed in vacuo. The crude material was purified by silica gel column chromatography, eluting with 0-100% EtOAc in DCM, to afford the title compound as an off-white solid (312 mg, 23%). 1H NMR (400 MHz, CDCl3): δ 10.00 (s, 1H), 8.04 (s, 2H), 7.81 (d, J=7.5 Hz, 1H), 7.72 (s, 1H), 7.52-7.42 (m, 2H), 7.13 (d, J=8.1 Hz, 1H), 6.91-6.85 (m, 2H), 6.62 (t, J=75.3 Hz, 1H), 6.05 (dd, J=9.9, 4.4 Hz, 1H), 3.85-3.76 (m, 2H), 3.72-3.59 (m, 2H), 3.49 (dd, J=14.0, 9.9 Hz, 1H), 3.18 (dd, J=14.0, 4.4 Hz, 1H), 1.32-1.19 (m, 1H), 0.70-0.63 (m, 2H), 0.40-0.34 (m, 2H). LCMS (Method 2): [MH+]=566 at 3.54 min.

Provenance & Evidence