Sodium Iodide → N,N-Diethylbenzamide

The crude 4-(N,N-diethylcarbamoyl)benzhydryl chloride (125 mmol) was dissolved in acetonitrile (300 mL). Sodium iodide (18.64 g, 125 mmol), diisopropylethylamine (32.65 mL, 187 mmol), and (+)-(2S,5R)-1-allyl-2,5-dimethylpiperazine (19.23 g, 125 mmol, prepared by the method described in Example 1 for (−)-(2R,5S)-1-allyl-2,5-dimethylpiperazine, but using di-p-toluoyl-L-tartaric acid as the resolving agent) were added. The mixture was stirred at reflux, under nitrogen, for 3 hours. The acetonitrile was removed under reduced pressure, the reaction mixture was poured into ethyl acetate (500 mL) and potassium carbonate solution (150 mL of a 2M aqueous solution), and shaken. The organic phase was separated, washed with water and brine, dried over solid potassium carbonate, and concentrated in vacuo to give 55.35 g (100% crude yield) of 4-((αR and αS)-α-((2R,S5)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide as a 1:1 mixture of isomers, epimeric at the benzhydryl carbon.

1. additionwere added
2. temperatureat reflux, under nitrogen, for 3 hours
3. customThe acetonitrile was removed under reduced pressure
4. additionthe reaction mixture was poured into ethyl acetate (500 mL) and potassium carbonate solution (150 mL of a 2M aqueous solution), and
5. stirringshaken
6. customThe organic phase was separated
7. washwashed with water and brine
8. dry with materialdried over solid potassium carbonate
9. concentrationconcentrated in vacuo

ORD record

ord-c863fda1b4ab44e7aa36d21ea263984f

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865721B2