N,N,N',N'-Tetramethylethylenediamine → HCID 14494149, compound

Temperature

0 °C

A solution of the compound of Example 8 (7.3 g, 20.3 mmol) and N,N,N',N'-tetramethylethylenediamine (1.65 mL, 10.9 mmol) in dry ether (120 ml) was cooled to 0° C. and treated with a solution of n-BuLi (2.5M) in hexane (17.5 mL, 43.8 mmol). The mixture was stirred at 0° C. for 0.5 hour and then at room temperature for an additional 1.5 hours. At this point the mixture was cooled to -78° C. A precooled solution of the compound of Example 5 (2.63 g, 18.8 mmol) in dry THF was then added by direct transfer via canula and the resulting mixture was stirred at -78° to -60° C. over 0.5 hour. The reaction was quenched by addition of saturated NH4Cl solution (40 mL) and was allowed to warm to room temperature. The mixture was diluted with ether and H2O. The ether layer was separated and concentrated to leave an oil which was taken up in a mixture of 1N HCl (200 mL) and THF (250 mL). The resulting solution was stirred at room temperature overnight. Following removal of most of the THF in vacuo, the solution was extracted twice with ether. The extracts were set aside for later recovery of unreacted compound of Example 5 while the aqueous layer was made basic by addition of solid NaOH and extracted twice again with ether. These extracts were combined, dried (Na2SO4) and concentrated in vacuo to leave a red oil. This was placed under high vacuum, warmed to remove α-methyl-benzenemethanamine and subjected to flash chromatography on silica gel. The column was initially eluted with CHCl3 to remove unwanted non-polar impurities. Subsequent elution with 2% and then 5% MeOH/CHCl3 provided, after removal of the solvents, the title compound (1.19 g, 26%).

1. waitat room temperature for an additional 1.5 hours
2. temperatureAt this point the mixture was cooled to -78° C
3. stirringthe resulting mixture was stirred at -78° to -60° C. over 0.5 hour
4. customThe reaction was quenched by addition of saturated NH4Cl solution (40 mL)
5. temperatureto warm to room temperature
6. additionThe mixture was diluted with ether and H2O
7. customThe ether layer was separated
8. concentrationconcentrated
9. customto leave an oil which
10. stirringThe resulting solution was stirred at room temperature overnight
11. customremoval of most of the THF in vacuo
12. extractionthe solution was extracted twice with ether
13. additionwas made basic by addition of solid NaOH
14. extractionextracted twice again with ether
15. dry with materialdried (Na2SO4)
16. concentrationconcentrated in vacuo
17. customto leave a red oil
18. temperaturewarmed
19. customto remove α-methyl-benzenemethanamine
20. washThe column was initially eluted with CHCl3
21. customto remove unwanted non-polar impurities
22. washSubsequent elution with 2%
23. custom5% MeOH/CHCl3 provided
24. customafter removal of the solvents

ORD record

ord-90b5a1018cbb4dfc925ddba36b174372

Source dataset

uspto-grants-1993_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05260309