Hydrogen Bromide → HCID 15521308, compound

Temperature

120 °C

A mixture of 2-phenylmethyl-1,4,7,10,13-penta(p-toluenesulfonyl)-1,4,7,10,13-pentaazacyclopentadecane prepared as in Example 6C (20.0 g, 0.0186 mole), phenol (8.75 g, 0.0929 mole) and 30% HBr in glacial acetic acid (250 ml) were heated in each of 2 sealed tubes in the dark at 120° C. for 16 h. Upon cooling to room temperature, a 1:1 mixture of ethanol and ethyl ether (250 ml) was added to each tube. The contents of the tubes were combined and ethyl ether (3 l) was added. The dark brown solid was filtered and washed thoroughly with ethyl ether. The oily solid was then dissolved in H2O (1 l) and the resulting solution was washed with ethyl ether. The solution was concentrated in vacuo to a volume of 250 ml. The pentahydrobromide salt was crystallized by the addition of isopropanol (1 l), followed by cooling to 5° C. The pentahydrobromide salt (21.2 g) was dissolved in H2O (50 ml) and the resulting solution was washed with ethyl ether. The pH of the solution was adjusted to 11 with 10N NaOH and the solvent was removed in vacuo. Ethanol (2×500 ml) was then added and removed in vacuo. The resulting brown oily solid was extracted with hot THF (2×500 ml) and filtered at room temperature. The filtrates were combined, the solvent was removed in vacuo and the oil was redissolved in THF. After filtration, the solvent was removed in vacuo. The residue was redissolved in a 1:1 mixture of CH3CN--THF and the solution was filtered. The solvent was removed in vacuo and the crude product was purified by recrystallization from cold CH3CN (-20° C.) to give 4.47 g (39% yield) of an off-white crystalline solid: mp 98-100° C.; 1H NMR (CDCl3) δ 1.75 (br s, 5 H), 2.35 (m, 1 H), 2.73 (m, 20 H), 7.22 (m, 5 H) ; Anal. calcd. for C17H31N5 : C, 66.84; H, 10.23; N, 22.93. Found: C, 66.86; H, 10.26; N, 23.32.

1. temperatureUpon cooling to room temperature
2. additionwas added to each tube
3. filtrationThe dark brown solid was filtered
4. washwashed thoroughly with ethyl ether
5. dissolutionThe oily solid was then dissolved in H2O (1 l)
6. washthe resulting solution was washed with ethyl ether
7. concentrationThe solution was concentrated in vacuo to a volume of 250 ml
8. customThe pentahydrobromide salt was crystallized by the addition of isopropanol (1 l)
9. temperatureby cooling to 5° C
10. dissolutionThe pentahydrobromide salt (21.2 g) was dissolved in H2O (50 ml)
11. washthe resulting solution was washed with ethyl ether
12. customthe solvent was removed in vacuo
13. additionEthanol (2×500 ml) was then added
14. customremoved in vacuo
15. extractionThe resulting brown oily solid was extracted with hot THF (2×500 ml)
16. filtrationfiltered at room temperature
17. customthe solvent was removed in vacuo
18. dissolutionthe oil was redissolved in THF
19. filtrationAfter filtration
20. customthe solvent was removed in vacuo
21. dissolutionThe residue was redissolved in a 1:1 mixture of CH3CN
22. filtrationTHF and the solution was filtered
23. customThe solvent was removed in vacuo
24. customthe crude product was purified by recrystallization from cold CH3CN (-20° C.)

ORD record

ord-cbe969a6c6a04524a7f2e8081fea3ede

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06084093