N-Methylbenzylamine → (1R,2R)-N,N,N'-triMethyl-1,2-diaMinocyclohexane

A solution of trans-2-dimethylaminocyclohexanol (61.1 g.; 0.427 mole) in 85 ml. of THF was added during 5 minutes to a suspension of NaH (17.97 g.; 0.427 mole of 57% dispersion in mineral oil) in 250 ml. of THF, and the mixture was heated at 95° for 2 hours. It was cooled to 10°, and treated dropwise with methanesulfonyl chloride (48.91 g.; 0.427 mole) during 40 minutes keeping the temperature at 15°.N-Methylbenzylamine (103.48 g.; 0.854 mole distilled) was then added, THF was evaporated and heating continued at 95° for 18 hours. The mixture was treated with 500 ml. of 20% NaOH, heated at 95°, cooled and extracted with ether (6×100 ml.). The ether solution was extracted with 10% HCl (6×100 ml.), backwashed with ether (discard ether), cooled, basified with 20% NaOH and extracted with ether. The ether extract was washed with H2O, saturated salt solution, dried (MgSO4) and evaporated to give 48.6 g. of crude N,N,N'-trimethyl-N'-benzyl-1,2-cyclohexanediamine as an oil. A solution of this oil (46.6 g.) was hydrogenated in two portions each in 130 ml. of EtOH, with 2.6 g. of 10% Pd-C and 28.6 g. of 70% HClO4 at initial pressure of 51 p.s.i. for 22 hours. The mixture was filtered through Celite, the filtrate was evaporated, cooled in ice and basified with 40% KOH. The resulting thick suspension was extracted with ether (4×200 ml.), the ether extract was dried (MgSO4) and evaporated. The product boiled at 87°-88° (15 mm.Hg). Vpc-mass spectrum showed that the first peak was 3.4 minutes, was N,N-dimethyl-1,2-cyclohexanediamine and the second peak the desired N,N,N'-trimethyl-1,2-cyclohexanediamine.

1. temperatureIt was cooled to 10°
2. customat 15°
3. customTHF was evaporated
4. temperatureheating
5. additionThe mixture was treated with 500 ml
6. temperatureof 20% NaOH, heated at 95°
7. temperaturecooled
8. extractionextracted with ether (6×100 ml.)
9. extractionThe ether solution was extracted with 10% HCl (6×100 ml.)
10. temperaturecooled
11. extractionextracted with ether
12. extractionThe ether extract
13. washwas washed with H2O, saturated salt solution
14. dry with materialdried (MgSO4)
15. customevaporated
16. customto give 48.6 g
17. waitfor 22 hours
18. filtrationThe mixture was filtered through Celite
19. customthe filtrate was evaporated
20. temperaturecooled in ice and basified with 40% KOH
21. extractionThe resulting thick suspension was extracted with ether (4×200 ml.)
22. extractionthe ether extract
23. dry with materialwas dried (MgSO4)
24. customevaporated
25. waitwas 3.4 minutes

ORD record

ord-3df16079274f49e989e429e720f75d85

Source dataset

uspto-grants-1979_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04148914