1,3-Adamantanedicarboxylic acid → 3-{[4-(2-tert-Butylphenyl)piperazin-1-yl]carbonyl}adamantane-1-carboxylic acid

Participants

Reaction Steps

A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (400 mg), 1,3-adamantanedicarboxylic acid (628 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (316 mg), 1-hydroxy-1H-benzotriazole monohydrate (253 mg), triethylamine (0.697 mL), and N,N-dimethylformamide (5 mL) was stirred at room temperature for over-night. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to purification by high performance liquid chromatography [Column: Gilson, Ltd. High throughput purification system, YMC Combiprep ODS-A, S-5 μm, 50 mm×20 mm; Gradient cycle: H2O (contains 0.1% CF3COOH)-acetonitrile (contains 0.1% CF3COOH), 90:10 (0 min)-90:10 (1 min)-10:90 (4.2 min)-10:90 (5.4 min)-90:10 (5.5 min)-90:10 (5.6 min); Flow rate: 25 mL/min; detection wavelength: UV 220 nm] to give the title compound (352 mg, 61%) as a white solid.

Provenance & Evidence