Hydrochloric Acid → Carbonic Acid

Participants

Reaction Conditions

Reaction Steps

Ethyl 4-{6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyrate (150 mg) is dissolved in a mixed solvent of ethanol (1 ml) and tetrahydrofuran (2 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (0.3 ml) and the mixture is stirred at 50° C. for 3 hours and 20 minutes. The reaction solution is cooled to room temperature and neutralized with a 2N-hydrochloric acid (0.3 ml), and thereto are added methylene chloride and a saturated brine and the mixture is separated, and the organic layer is concentrated under reduced pressure. The resulting residue is purified by LCMS (column: CAPCELPACK MG2 C18, eluate: a 10 μM aqueous carbonic acid solution/acetonitrile=55/45→40/60) to give 4-{6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyric acid (31.4 mg). The resulting carboxylic acid is dissolved in ethanol (1 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (42 μl) and the reaction solution is concentrated under reduced pressure to give 4-{6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyric acid sodium salt (30.6 mg). MS (m/z): 727 [M−Na]−

Provenance & Evidence