반응 #1105500

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5-(2-adamantan-1-yl-ethyl)-2-(2-fluoro-phenyl)-1H-imidazole-4-carboxylic acid

β-alanine benzyl ester p-toluenesulfonate

N,N-diisopropylethylamine

bromo-tris-pyrrolidino-phosphonium hexafluorophosphate

→

product

수율 58.0%

3-{[5-(2-Adamantan-1-yl-ethyl)-2-(2-fluoro-phenyl)-1H-imidazole-4-carbonyl]-amino}-propionic Acid Benzyl Ester

수율 58.0%

용매

DCM

DCM

반응 조건

후처리

1. 1
   세척washed with 5% aqueous potassium hydrogen sulphate and with saturated sodium hydrogen carbonate
2. 2
   건조The organic phase was dried (MgSO4)
3. 3
   기타the solvent was evaporated
4. 4
   기타The residue was purified by flash column chromatography (silica, DCM/ethyl acetate 9:1)

실험 절차

To a solution of 5-(2-adamantan-1-yl-ethyl)-2-(2-fluoro-phenyl)-1H-imidazole-4-carboxylic acid (Example 50) (200 mg, 0.50 mmol) and β-alanine benzyl ester p-toluenesulfonate (175 mg, 0.50 mmol) in DCM (5 ml) was added N,N-diisopropylethylamine (0.26 ml, 1.50 mmol), 4-dimethylaminopyridine (cat.) and bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) (230 mg, 0.50 mmol). The solution was kept at room temperature for 16 h, diluted with DCM (10 ml), washed with 5% aqueous potassium hydrogen sulphate and with saturated sodium hydrogen carbonate. The organic phase was dried (MgSO4) and the solvent was evaporated. The residue was purified by flash column chromatography (silica, DCM/ethyl acetate 9:1) to afford the product as colourless foam (153 mg, 58%). 1H NMR (300 MHz, CDCl3) 9.72 (1H, br s), 8.23 (1H, m), 7.68 (1H, t), 7.37-7.15 (8H, m), 5.17 (2H, s), 3.73 (2H, m), 3.07 (2H, m), 2.72 (2H, m), 1.97 (3H, s), 1.73-1.41 (14H, m).

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