Sodium Hydroxide → 2'-Chloro-3'-fluoro-2-(methoxymethyl)biphenyl-4-carboxylic acid

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Reaction Steps

A 5N aqueous solution of NaOH (2.3 mL, 11.5 mmol) was added into a solution of methyl 2′-chloro-3′-fluoro-2-(methoxymethyl)biphenyl-4-carboxylate (2.38 g, 7.7 mmol) in EtOH (25 mL) and heated at reflux for 30 minutes. The reaction mixture was concentrated under vacuum. The residue was taken up with water (30 mL) and a 5N aqueous solution of HCl (4 mL), and then extracted with MTBE (100 mL, then 50 mL). The organic layers were washed with brine, combined, dried (MgSO4) and treated with activated charcoal. After filtration through a Celite pad, the solution was concentrated under vacuum. After purification by crystallization from a mixture of MTBE and heptane, the title compound was obtained as a white powder (2.01 g, 88%). HPLC (Method A) Rt 4.1 min (Purity: 99.5%). LC/MS (Method B): 293.0 (M−H)−. 1H NMR (DMSO-d6, 300 MHz) δ 13.13 (s, 1H), 8.10 (d, J=1.7 Hz, 1H), 7.94 (dd, J=8.0, 1.7 Hz, 1H), 7.54-7.44 (m, 2H), 7.33 (d, J=8.0 Hz, 1H), 7.23-7.18 (m, 1H), 4.23 (d, J=12.7 Hz, 1H), 4.15 (d, J=12.7 Hz, 1H), 3.17 (s, 3H).

Provenance & Evidence