Hydrochloric Acid → 2''-{[(4S,5R)-5-(3-chloro-4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Participants

Reaction Steps

To a 0° C. solution of benzyl[(1S,2R)-2-(3-chloro-4-fluorophenyl)-2-hydroxy-1-methylethyl]carbamate (51.4 mg, 0.152 mmol) in DMA (1.5 mL) was added NaHMDS (0.296 mL of a 1M solution in THF, 0.296 mmol). After 5 minutes, a solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (75 mg, 0.152 mmol) in DMA (2.5 mL) was added via cannula. After 5 minutes, saturated aqueous NaOH solution (3 mL) was added, and the mixture was allowed to warm to room temperature. After 3 hours, the mixture was acidified with 6 N HCl and concentrated. The residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) to afford 2″-{[(4S,5R)-5-(3-chloro-4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS=627.9 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.95-7.62 (m, 2H), 7.69-7.52 (m, 2H), 7.43-7.37 (m, 2H), 7.30-7.24 (m, 1H), 7.18-7.11 (m, 2H), 7.08-6.86 (m, 3H), 5.44 (d, J=8.0 Hz), 5.18 (d, J=8.0 Hz), 4.92-4.85 (m, 1H), 4.18 (d, J=15.5), 3.96 (d, J=15.5), 3.93-3.85 (m, 3H), 3.73-3.66 (m, 1H), 2.36 (s), 2.32 (s), 0.55 (d, J=6.6 Hz), 0.44 (d, J=6.6 Hz).

Provenance & Evidence