Yield:474010-60-1 81%

Reaction Conditions:

Stage #1: (R)-2-methylpiperazine dihydrochloridewith potassium carbonate in acetonitrile at 70; for 18 h;
Stage #2: benzoyl chloride in acetonitrile at 3 - 20; for 20.5 h;

Steps:

9

To a slurry of (R)-2-methylpiperazine dihydrochloride (300 g, 1.73 mol) in acetonitrile (2.6 L) was added potassium carbonate (479 g, 3.46 mol) with stirring under nitrogen. The reaction was then heated to 70 ⁰C for 18 hours. The reaction was then cooled to room temperature and the inorganic slurry was filtered and washed with acetonitrile (0.9 L). The filtrate was then cooled to 3 ⁰C with stirring under nitrogen. To this solution was added benzoyl chloride (221 ml, 1.90 mol) over 2.5 hours maintaining the temperature below 10 ⁰C. The reaction was allowed to warm to room temperature and stirred for 18 hours. The resultant slurry was then cooled to 3 ⁰C and then filtered under vacuum. The filter cake was washed with acetonitrile (300 ml) and was then dried under vacuum at 60 ⁰C overnight to give the title compound as a white crystalline solid (336 g, 1.40 mol, 81% yield). ¹H-NMR (d₄-methanol, 300 MHz), δ: 1.36 (3 H, s, br), 3.19-3.32 (2 H, m), 3.40- 3.50 (4 H, m), 4.79 (2 H, s), 7.51 (5 H, s).

References:

WO2006/85199,2006,A1 Location in patent:Page/Page column 29