反应详情

温度

10 °C

Oxalyl chloride (43.0 mL, 0.492 mol) was added dropwise to a suspension of 5-(p-cyanophenyl)pentanoic acid in 100 mL of dry 1,2-dichloroethane at 23° C. under a nitrogen atmosphere. After 5 min, 50 mL of DMF was added. After 30 min, the reaction was concentrated in vacuo. The residue was dissolved in anhydrous THF (150 mL) under a nitrogen atmosphere. Azidotrimethylsilane (14.6 mL, 0.110 mL) was added dropwise at 23° C. After 5 min, the reaction was warmed to achieve reflux for 1 hour. The reaction was cooled to 10° C. and concentrated HCl (20 mL) was added over 1 min. The cooling bath was removed and stirring was continued for 15 min. The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate (200 mL) and water (200 mL). The aqueous layer was basified with 1N NaOH (250 mL) and extracted with ethyl acetate (2×200 mL). The organic layer was washed with water (100 mL) followed by brine (100 mL), and dried (Na2SO4). After concentration in vacuo, the residue was diluted with ethyl acetate:methanol (150 mL:5 mL) and treated with anhydrous HCl in dioxane (6.9N) at 0° C. The resultant precipitate was filtered, washed with ethyl acetate then ether. The solid was dried (atmospheric pressure; 55° C.) to afford 14.3 g: m.p. 155°-160° C.

1. waitAfter 30 min
2. concentrationthe reaction was concentrated in vacuo
3. dissolutionThe residue was dissolved in anhydrous THF (150 mL) under a nitrogen atmosphere
4. additionAzidotrimethylsilane (14.6 mL, 0.110 mL) was added dropwise at 23° C
5. waitAfter 5 min
6. temperaturethe reaction was warmed
7. temperatureto achieve reflux for 1 hour
8. additionconcentrated HCl (20 mL) was added over 1 min
9. customThe cooling bath was removed
10. waitwas continued for 15 min
11. concentrationThe reaction was concentrated in vacuo
12. customthe residue was partitioned between ethyl acetate (200 mL) and water (200 mL)
13. extractionextracted with ethyl acetate (2×200 mL)
14. washThe organic layer was washed with water (100 mL)
15. dry with materialdried (Na2SO4)
16. concentrationAfter concentration in vacuo
17. additionthe residue was diluted with ethyl acetate
18. additionmethanol (150 mL:5 mL) and treated with anhydrous HCl in dioxane (6.9N) at 0° C
19. filtrationThe resultant precipitate was filtered
20. washwashed with ethyl acetate
21. customThe solid was dried (atmospheric pressure; 55° C.)
22. customto afford 14.3 g