Triethylamine → 1-Benzyl-3-[((9Z,12Z)-Octadeca-9,12-Dienyl)Oxy]-4-Octyloxy-Pyrrolidine

Temperature

50 °C

In 500 mL 3N RBF, compound 1 (18 g, 51.2 mmol) and triethylamine (0.714 ml, 5.12 mmol) were suspended in 180 mL toluene for addition of the sodium hydride (4.30 g, 108 mmol). Heated suspension to 50° C. for 1 h. Cooled back to 23° C. and then added the n-octyl mesylate (10.67 g, 51.2 mmol). Heated slurry up to 80° C. for 18 h. Cooled to 23° C. and poured into 200 mL 1M K2CO3. Extracted with methyl tert-butyl ether (MTBE) and then dried combiend layers over Na2SO4. Filtered, concentrated and purified oil by silica gel chromatogtaphy to obtain 7.22 g of a slightly yellow oil. In 500 mL 3N RBF, 4.04 g of the aforementioned oil (13.23 mmol) and triethylamine (0.184 ml, 1.323 mmol) was dissolved in 80 mL toluene for addition of the sodium hydride (0.582 g, 14.55 mmol). Heated suspension to 50° C. for 1 h. Cooled back to 23° C. and then added the linoleoyl mesylate (5.01 g, 14.55 mmol). Heated slurry up to 80° C. for 21 h or until complete disappearance of the starting material was observed by HPLC. Cooled to 23° C., diluted with 100 mL hexane and washed with 100 mL 1M K2CO3. Extracted aquoues layer with 100 mL hexane and then washed combined organic layers with 100 mL brine and dried over MgSO4. Filtered and concentrated. Purified by silica gel chromatography to obtain 5.02 g of 2 as a clear oil (33% yield over 2 steps). 1H NMR (400 MHz, CDCl3) δ7.28 (m, 5H), 5.40 (m, 4H), 3.85 (Ψt, J=4.8 Hz, 2H), 3.61 (m, 2H), 3.42 (m, 4H), 2.88 (dd, J=9.7, 6.1 Hz, 2H), 2.79 (Ψt, J=6.4 Hz, 2H). 2.51 (dd, J=10.1, 4.2 Hz, 21-1), 2.06 (q, J=6.7 Hz, 2H), 1.56 (q, 4H), 1.41-1.29 (m, 26H), 0.9 (m, 6H).

1. temperatureCooled back to 23° C.
2. temperatureHeated slurry up to 80° C. for 18 h
3. temperatureCooled to 23° C.
4. extractionExtracted with methyl tert-butyl ether (MTBE)
5. dry with materialdried combiend layers over Na2SO4
6. filtrationFiltered
7. concentrationconcentrated
8. custompurified oil by silica gel chromatogtaphy
9. customto obtain 7.22 g of a slightly yellow oil
10. temperatureHeated suspension to 50° C. for 1 h
11. temperatureCooled back to 23° C.
12. temperatureHeated slurry up to 80° C. for 21 h
13. temperatureCooled to 23° C.
14. washwashed with 100 mL 1M K2CO3
15. washExtracted aquoues layer with 100 mL hexane and then washed
16. dry with materialdried over MgSO4
17. filtrationFiltered
18. concentrationconcentrated
19. customPurified by silica gel chromatography

ORD record

ord-b1abdd26e81847f99878d70d00ff1bf8

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067882B2