Trityl chloride → HCID 58914637, compound

Malononitrile (37.6 g, 0.57 mol), sodium azide (37.0 g, 0.57 mol), ammonium chloride (30.2 g, 0.57 mol), and DMF (400 mL) were charged to a reaction vessel. The vessel was placed under a nitrogen gas purge, equipped with a thermocouple, and stirred with a mechanical stirrer at room temperature for 30 minutes. The thick slurry was heated to 80° C. and stirred at that temperature for 2 h. 1H NMR analysis of a sample showed the reaction to be complete. The mixture was cooled to ambient temperature, at which time triethylamine (159 mL, 1.14 mol) and trityl chloride (159 g, 0.57 mol) were added. The mixture was stirred for 16 hours at ambient temperature. TLC analysis showed that the reaction had gone to completion. The reaction mixture was filtered through a fritted funnel and the solids (NH4Cl salts) were washed with ethyl acetate (1.5L×2). The organic layer was washed with H2O (1L×3) and the aqueous portions were combined and extracted with another part of ethyl acetate (1L). The two organic portions were combined and washed with water (1L), brine, and dried with MgSO4. The sample was concentrated in vacuo to a brown solid. A crude 145 grams of material was added to 400 mL of ethyl acetate and heated to reflux. n-Hexanes (400 mL) was added to the hot solution dropwise over 15 min with continued refluxing. The solution became cloudy and was then cooled slowly to ambient temperature as a granular solid precipitated from the solution. The granular solid was collected with a fritted funnel and dried in a vacuum oven for 16 h. Low yields for this reaction prompted us to reexamine the NH4Cl salts that were filtered away during the first step of purification. The salts were slurried with ethyl acetate (600 mL) for several minutes. The solids were filtered once again, washed with ethyl acetate, and the organic mother liquor was concentrated in vacuo to a white solid. The two batches of clean product were combined to give 135 grams (0.38 mol, 69% yield) of (2-trityl-2H-tetrazol-5-yl)-acetonitrile. 1H NMR (CDCl3): 4.06 (s, 2H), 7.09 (m, 6H), 7.36 (m, 9H). Anal. Caldc. for C22H17N5: C, 75.19; H, 4.83; N, 19.93. Found: C, 75.11; H, 4.98; N, 20.06.

1. custompurge
2. customequipped with a thermocouple
3. temperatureThe thick slurry was heated to 80° C.
4. stirringstirred at that temperature for 2 h
5. customthe reaction
6. additionwere added
7. stirringThe mixture was stirred for 16 hours at ambient temperature
8. filtrationThe reaction mixture was filtered through a fritted funnel
9. washthe solids (NH4Cl salts) were washed with ethyl acetate (1.5L×2)
10. washThe organic layer was washed with H2O (1L×3)
11. extractionextracted with another part of ethyl acetate (1L)
12. washwashed with water (1L), brine
13. dry with materialdried with MgSO4
14. concentrationThe sample was concentrated in vacuo to a brown solid
15. additionA crude 145 grams of material was added to 400 mL of ethyl acetate
16. temperatureheated to reflux
17. additionn-Hexanes (400 mL) was added to the hot solution dropwise over 15 min with continued refluxing
18. temperaturewas then cooled slowly to ambient temperature as a granular solid
19. customprecipitated from the solution
20. customThe granular solid was collected with a fritted funnel
21. customdried in a vacuum oven for 16 h
22. customLow yields for this reaction
23. filtrationwere filtered away during the first step of purification
24. waitThe salts were slurried with ethyl acetate (600 mL) for several minutes
25. filtrationThe solids were filtered once again
26. washwashed with ethyl acetate
27. concentrationthe organic mother liquor was concentrated in vacuo to a white solid

ORD record

ord-0c90ca083c8b425585e564ab89d37040

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07250433B2