To a solution of 4-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]piperidine (D120) (200 mg, 0.452 mmol) in Acetonitrile (10 mL) was added DBU (0.205 mL, 1.357 mmol) and ethyl 2-propenoate (136 mg, 1.357 mmol). The reaction solution was heated to 60° C. for 2 h. The reaction solution was concentrated and the residue was hydrolized with a solution of NaOH (4.52 mL, 2.262 mmol) in water. The reaction mixture was neutralized with 2N HCl till pH ˜6.0. The mixture was extracted with EA/THF for 3 times. The combined organic layers were concentrated and purified by Mass Directed AutoPrep to afford 3-{4-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]-1-piperidinyl}propanoic acid (E95) (12 mg) as a TFA salt.
