1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid ethyl ester

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Reaction Steps

(R)-ethyl 5-(3-piperidinyl)-2-methylbenzoate-D-tartaric acid (Example 9; 2.13 g, 5.36 mmol) was dissolved in 100 mL ethyl acetate and washed with 100 mL saturated aqueous NaHCO3. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The resultant oil was taken up in 20 mL CH2Cl2 and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (2.05 g, 10.72 mmol) and 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylic acid (1.69 g, 5.90 mmol) were added. The reaction was stirred at ambient temperature under nitrogen for 72 h. The reaction was diluted with 200 mL diethyl ether and washed with water (100 mL), saturated aqueous NaHCO3 (2×100 mL), 0.5 N HCl (2×100 mL), water (100 mL), and brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure to yield (R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid ethyl ester (2.62 g, 95%) as a clear oil.

Provenance & Evidence