反应详情

2-(4-methylsulfanyl-phenoxy)-nicotinic acid (3.0 g, 11.5 mmol) was dissolved in dimethylformamide (60 ml) and triethylamine (4.8 ml, 34.4 mmol) was added followed by cis-4-Amino-cyclohexanecarboxylic acid benzyl ester mesylate (4.66 g, 11.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.42 g, 12.6 mmol) and 1-hydroxybenzotriazole (1.71 g, 12.6 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between sat. sodium bicarbonate solution (50 ml) and ethyl acetate (50 ml) and the aqueous phase was extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with water (25 ml), brine (25 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with ethyl acetate:pentane (1:1, by volume) to give cis-4-{[2-(4-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexanecarboxylic acid benzyl ester (4.75 g) as a white solid.

1. customthe solvent was removed under reduced pressure
2. customThe residue was partitioned between sat. sodium bicarbonate solution (50 ml) and ethyl acetate (50 ml)
3. extractionthe aqueous phase was extracted with ethyl acetate (3×100 ml)
4. washThe combined organic extracts were washed with water (25 ml), brine (25 ml)
5. dry with materialdried over MgSO4
6. customthe solvent was removed under reduced pressure
7. customThe residue was purified by flash column chromatography on silica gel eluting with ethyl acetate:pentane (1:1, by volume)