Diisopropylethylamine → {3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-[4-(2,2,2-trifluoroethyl)phenyl]piperidin-1-yl}-(thiomorpholin-4-yl)methanone

Participants

Reaction Steps

To a solution of 600 mg (1.08 mmol, purity 75%) of the carboxylic acid from Example 56A in 20.0 ml of N,N-dimethylformamide were added, at RT, 657 mg (1.73 mmol) of HATU and 0.57 ml (419 mg, 3.24 mmol) of N,N′-diisopropylethylamine, and the mixture was stirred for 30 min. Subsequently, the mixture was admixed with 225 mg (1.84 mmol, purity 85%) of ethyl W-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] and then stirred at room temperature for 2 h. The reaction solution was purified directly by means of preparative HPLC. The resulting intermediate was taken up in toluene (68 ml), admixed with 4 Å molecular sieve and stirred under reflux for 2 days. The reaction solution was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by means of preparative HPLC. Yield: 320 mg (61% of theory)

Provenance & Evidence