Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-4-Boc-piperazin-1-ylacetamide

Temperature

-78 °C

N-Methoxy-N-methylamine hydrochloride (4.3 g, 44.1 mmol) was dissolved in methylene chloride (25 mL). The solution was cooled to −78° C., and a solution of trimethylaluminum (44.1 mL, 44.1 mmol, 1 M in heptane) was slowly added. The mixture was stirred at 0° C. for 30 min and was allowed to warm to room temperature and stirred for 30 min. The mixture was then cooled to 0° C., and a solution of ethyl 4-Boc-piperazin-1-ylacetate (10 g, 36.8 mmol) was added dropwise. After 15 min, the cold bath was removed and stirring continued overnight. The mixture was diluted with ethyl acetate and water. The layers were separated, and the water layer extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (Na2SO4), filtered, and concentrated to provide N-methoxy-N-methyl-4-Boc-piperazin-1-ylacetamide as a light yellow oil (6.02 g, 57%) that solidified upon standing. The product was used without further purification.

1. temperatureto warm to room temperature
2. stirringstirred for 30 min
3. temperatureThe mixture was then cooled to 0° C.
4. waitAfter 15 min
5. customthe cold bath was removed
6. stirringstirring continued overnight
7. additionThe mixture was diluted with ethyl acetate and water
8. customThe layers were separated
9. extractionthe water layer extracted with ethyl acetate
10. washwashed with brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-57856b496b5049949f7ac709b2e74051

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06946467B2