Tetrahydrofuran → HCID 56644366, compound

Participants

Reaction Steps

BOP-Cl (33.4 mg, 0.131 mmol) was added to a mixture of (3S)-ethyl 1-(2-hydroxy-2-(4-(N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidine-3-carboxylate (Intermediate 3, 40 mg, 0.119 mmol), 3-(1-(3,5-dichlorophenyl)cyclohexyl)propanoic acid (35.9 mg, 0.119 mmol), and diisopropylethyl amine (0.042 mL, 0.239 mmol) in DMF (3 mL). The mixture was stirred at room temperature for 2 h, and a 1M solution of tetra-n-butylammonium fluoride in THF (0.119 mL, 0.119 mmol) was added. The mixture was heated to 80° C. overnight, diluted with ethyl acetate, and washed with saturated aqueous NaCl solution. The organic layer was dried (MgSO4), filtered and concentrated. The crude product was dissolved in acetonitrile (3 mL), treated with 6 N aq. HCl solution and heated to 50° C. overnight. The mixture was filtered, and purified by HPLC (HPLC conditions: Phenomenex Luna C18 5 micron column (250×30 mm); 25-100% AcCN/water (0.1% TFA); 25 minute gradient; 30 mL/min). Isolated fractions with the correct mass were collected and freeze-dried overnight to obtain (3S)-1-(2-(4-(5-(2-(1-(3,5-dichlorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)phenyl)-2-hydroxyethyl)-3-piperidinecarboxylic acid (52 mg, 63% yield) as a white solid. HPLC retention time=3.75 minutes (Waters Sunfire C18 4.6×50 mm) eluting with 10-90% aqueous methanol with 0.1% TFA over a 4 minute gradient. LC/MS: m/e 572.16, 574.10 (M+H)+.

Provenance & Evidence