Acetic Acid → 1-{2-[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-methylphenyl]ethyl}-4-piperidinecarboxylic acid

Participants

Reaction Steps

To a solution of [3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-methylphenyl]acetaldehyde (D106) (120 mg, 0.310 mmol) in Dichloromethane (DCM) (20 mL) stirred at room temperature was added ethyl 4-piperidinecarboxylate (195 mg, 1.241 mmol) and AcOH (0.15 mL, 2.62 mmol). The reaction mixture was stirred at room temperature for 10 min, and sodium triacetoxyborohydride (131 mg, 0.620 mmol) was added. The reaction mixture was continuously stirred overnight. The reaction was quenched with water and DCM was evaporated in vacuo. The residue was dissolved in Isopropanol (8 mL), and sodium hydroxide (50 mg, 1.250 mmol) was added. The reaction was stirred for 2 hours. 1M HCl solution was added until pH=6-7. Isopropanol was removed. The mixture was extracted by EA/THF/MeCN for 3 times. The combined organic solution was washed with brine. The solution was concentrated and purified by Mass Directed AutoPrep to afford 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-methylphenyl]ethyl}-4-piperidinecarboxylic acid (E74) (35 mg) as a off-white solid. δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 1.55 (2H, m), 1.81 (2H, m), 2.05 (2H, m), 2.19 (1H, m), 2.46 (3H, s), 2.50 (2H, m), 2.87 (4H, m), 4.86 (1H, dt), 7.26 (1H, m), 7.36 (2H, m), 7.68 (1H, d), 8.02 (1H, dd), 8.14 (1H, d), 12.18 (1H, br. s.). MS (ES): C26H30ClN3O3S requires 499.2. found 500.2 (M+H+).

Provenance & Evidence