Imidazole → HCID 67456713, compound

[3′-(3-Cyanopropyl)biphenyl-4-yl]methanol (0.44 g) and imidazole (0.30 g) were dissolved in N,N-dimethylformamide (4.3 mL), chlorotriisopropylsilane (0.45 mL) was added, and the resulting mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium hydrogen carbonate (10 mL) was added to the reaction mixture and the whole was extracted with diethyl ether (40 mL). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (7.3 mL) and added dropwise to a solution of lithium alminium hydride (0.1 g) in tetrahydrofuran (10 mL) under ice-cooling, and the resulting mixture was stirred at room temperature for 4 hours. The reaction was quenched by sequential addition of water (0.1 mL), 15% aqueous sodium hydroxide (0.1 mL) and water (0.1 mL). The insoluble material was filtered out and the filtrate was concentrated under reduced-pressure. The residue obtained was dissolved in tetrahydrofuran (6.9 mL), N-carbobenzoxyoxysuccinimide (0.45 g) was added, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography on aminopropylated silica gel (eluent: hexane/ethyl acetate=2/1) to give the title compound as triisopropylated form. The compound obtained was dissolved in tetrahydrofuran (4.1 mL), 1 mol/L tetrabutylammonium fluoride-tetrahydrofuran solution (1.1 mL) was added, and the resulting mixture was stirred at room temperature for 1.5 hours. Saturated aqueous ammonium chloride (10 mL) was added to the reaction mixture and the whole was extracted with ethyl acetate (40 mL). The organic layer was washed with brine (15 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the'title compound (0.40 g).

1. extractionthe whole was extracted with diethyl ether (40 mL)
2. washThe organic layer was washed with brine (10 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in tetrahydrofuran (7.3 mL)
6. additionadded dropwise to a solution of lithium alminium hydride (0.1 g) in tetrahydrofuran (10 mL) under ice-
7. temperaturecooling
8. stirringthe resulting mixture was stirred at room temperature for 4 hours
9. customThe reaction was quenched by sequential addition of water (0.1 mL), 15% aqueous sodium hydroxide (0.1 mL) and water (0.1 mL)
10. filtrationThe insoluble material was filtered out
11. concentrationthe filtrate was concentrated under reduced-pressure
12. customThe residue obtained
13. stirringthe resulting mixture was stirred at room temperature for 3 hours
14. concentrationThe reaction mixture was concentrated under reduced pressure
15. customthe residue was purified by column chromatography on aminopropylated silica gel (eluent: hexane/ethyl acetate=2/1)

ORD record

ord-ad00ee02c27846b7811dff5f0b2a838a

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07795236B2