反应详情

Triethylamine (5.2 mL) and magnesium chloride (4.3 g) were added to dry acetonitrile (30 mL) solution of cyanoacetic acid (1.6 g), and the mixture was vigorously stirred at room temperature for 23 hours under an atmosphere of argon. Next, a catalytically effective amount of N,N-dimethylaminopyridine and 1,1′-carbonyldiimidazole (1.34 g) were added to anhydrous tetrahydrofuran (20 mL) suspension of 2-(2-phenylethyl)benzimidazole-4-carboxylic acid (2.0 g) obtained in Reference Example 3, and the mixture was stirred for 2.5 hours under an atmosphere of argon. The reaction solution was added to the previously prepared cyanoacetic acid suspension of magnesium salt while cooling in an ice bath, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ice water (30 mL) and, at the same temperature, adjusted to pH 1 with 4 N hydrochloric acid. At the same temperature, this was adjusted to pH 9 with saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) and the desired fraction was concentrated to obtain the title compound as colorless crystal (1.03 g).

1. customobtained in Reference Example 3
2. stirringthe mixture was stirred for 2.5 hours under an atmosphere of argon
3. temperaturewhile cooling in an ice bath
4. stirringthe mixture was stirred at room temperature for 2 hours
5. extractionextracted with ethyl acetate
6. washThe organic layer was washed with water and brine
7. dry with materialdried over anhydrous sodium sulfate
8. customthe solvent was evaporated under a reduced pressure
9. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
10. concentrationthe desired fraction was concentrated