Ethyl bromoacetate → (4-Methylpiperazin-1-yl)acetic acid

Dissolve N-methylpiperazine (5.0 mL, 45.09 mmol) in diethyl ether in a stoppered flask and treat with neat ethyl bromoacetate (3.012 g, 18.036 mmol). Stir the reaction mixture at room temperature overnight, filter and wash the filter cake with diethyl ether. Combine the organic filtrates and evaporate the solvent in vacuo to give a light yellow oil. Take up in water (60 mL) and heat at 95° C. for 4 hours, allow to cool to room temperature and stir overnight. Evaporate the solvent in vacuo and dissolve the residue in acetonitrile and evaporate the solvent in vacuo (twice) to azeotrope residual water. Dissolve in a minimal amount of methanol, dilute with diethyl ether and place in the freezer. Isolate the crystals which form by decanting the supernatant and wash with diethyl ether. Obtain two more crops of crystals from the mother liquor to give 4-methylpiperazine-1-acetic acid (2.345 g, 82%); mp 158°-160° C. (lit 159.5°-161° C.), 1H NMR (D2O) δ3.98 (s, 2), 3.81-3.32 (m, 8), 2.89 (s, 3).

1. filtrationfilter
2. washwash the filter cake with diethyl ether
3. customevaporate the solvent in vacuo
4. customto give a light yellow oil
5. temperatureheat at 95° C. for 4 hours
6. temperatureto cool to room temperature
7. stirringstir overnight
8. customEvaporate the solvent in vacuo
9. dissolutiondissolve the residue in acetonitrile
10. customevaporate the solvent in vacuo (twice)
11. dissolutionDissolve in a minimal amount of methanol
12. additiondilute with diethyl ether and place in the freezer
13. customIsolate the crystals which form
14. customby decanting the supernatant
15. washwash with diethyl ether
16. customObtain two more crops of crystals from the mother liquor

ORDレコード

ord-f94fa9efe00e46998bade837de146bfb

出典データセット

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05624921