To an ice-cold solution of cis-4-(trifluoromethyl)cyclohexanecarboxylic acid (267 mg, 1.36 mmol) in dichloromethane (5 mL), oxalyl chloride (0.18 mL, 2.04 mmol) and several drop of N,N-dimethylformamide were added. After being stirred at room temperature for 1 h, the mixture was concentrated in vacuo to give a waxy solid. The residual solid was dissolved with dichloromethane (3 mL) and added to the mixture of (R)-3-(pyrrolidin-2-ylmethoxy)picolinamide dihydrochloride (200 mg, 0.68 mmol, EXAMPLE 1 Step 3) and triethylamine (0.48 mL, 3.40 mmol) in dichloromethane (5 mL) at 0° C. After being stirred at 0° C. for 2 h, the mixture was dissolved with ethyl acetate and 2 N hydrochloric acid. The aqueous layer was washed with ethyl acetate, and basified with aq. ammonia. The mixture was extracted with ethyl acetate twice, and washed with brine. The combined extracts were dried over sodium sulfate and concentrated in vacuo to give an amber oil. The residual oil was purified by preparative TLC (methanol/dichloromethane 1:10) to afford 160 mg of the title compound as a colorless viscous oil.
