Hydrochloric Acid → HCID 22279782, compound

[4-(5-Phenylpent-1-ynyl)thiophen-2-yl]acetonitrile (321 g, 12.1 mmol) obtained in Example 25(c) was dissolved in ethanol (15 ml), and potassium hydroxide (1.70 g, 30.2 mmol) in water (15 ml) was added thereto in an ice bath followed by heating under reflux for 2 hours. After the reaction solution was acidified with 1N hydrochloric acid, the resulting solution was extracted with ethyl acetate. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (15 ml), and triethylamine (1.69 ml, 12.1 mmol) was added thereto. To the reaction solution was added dropwise ethyl chloroformate (1.21 ml, 12.7 mmol) in tetrahydrofuran (15 ml) in an ice bath, and the reaction mixture was stirred for 30 minutes under cooling with ice in a nitrogen atmosphere. After this reaction solution was filtered, the obtained filtrate was added slowly to an aqueous solution (10 ml) of sodium borohydride (2.29 g, 60.5 mmol) in an ice bath, and then the mixture was stirred for 3 days at room temperature. After the reaction solution was cooled down, acidified with 1N hydrochloric acid, and the resulting solution was extracted with ethyl acetate, and then the ethyl acetate layer was washed with a 1N aqueous sodium hydroxide solution and then with a saturated aqueous sodium chloride solution The ethyl acetate layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The residue was purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=10:1-4:1) to afford the title compound (2.74 g, 84% yield).

1. customin an ice bath followed
2. temperatureby heating
3. temperatureunder reflux for 2 hours
4. extractionthe resulting solution was extracted with ethyl acetate
5. dry with materialAfter the ethyl acetate layer was dried over anhydrous sodium sulfate
6. customthe solvent was evaporated under reduced pressure
7. dissolutionThe obtained residue was dissolved in tetrahydrofuran (15 ml)
8. temperatureunder cooling with ice in a nitrogen atmosphere
9. filtrationAfter this reaction solution was filtered
10. stirringthe mixture was stirred for 3 days at room temperature
11. temperatureAfter the reaction solution was cooled down
12. extractionthe resulting solution was extracted with ethyl acetate
13. washthe ethyl acetate layer was washed with a 1N aqueous sodium hydroxide solution
14. dry with materialwith a saturated aqueous sodium chloride solution The ethyl acetate layer was dried over anhydrous sodium sulfate
15. customthe solvent was evaporated in vacuo
16. customThe residue was purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=10:1-4:1)

ORD record

ord-f43bc21bf15245409b1cffe7d9d9f7d2

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06723745B2