Water → 1-[2-(2,4,5-Trifluorophenoxy)ethyl]-3-(4-methyl-1-piperazinyl)-2(1H)-pyrazinone

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(4-methyl-1-piperazinyl)-2(1H)-pyrazinone (obtained in Step 2 above; 0.5 g, 2.6 mmol) and t-BuOK (440 mg, 3.90 mmol) in THF (40 mL) was stirred until the mixture became thick (about 10 min), and then a solution of 2-(2,4,5-trifluorophenoxy)ethyl methanesulfonate (0.90 g, 2.2 mmol; from Step 4) in THF (10 mL) was added. After being stirred for 5 days at ambient temp, HPLC showed only 50% conversion. The reaction solution was then heated to 60° C. overnight which gave almost full conversion. The reaction was worked up according to the following: water was added, THF was evaporated off and the aqueous mixture was extracted twice with EtOAc, dried (Na2SO4) and concentrated to yield 1.08 g of the crude product as a yellow oil. Purification by chromatography on silica gel [eluent: 2% MeOH in CHCl3+NH3 (g)] gave the title compound as a yellow oil, which solidified upon cooling. Yield: 304 mg (32%). HPLC purity: 100%. MS m/z 369 (M+H)+. HRMS m/z calcd for C17H19F3N4O2 (M)+ 368.1460, found 368.1462.

Provenance & Evidence