ethyl 2-piperazin-1-ylacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl piperazine-1-acetate (680 mg, 3.71 mmol) in tetrahydrofuran (8.0 mL) was mixed with triethylamine (0.776 mL, 5.57 mmol) and thiocarbonyldiimidazole (992 mg, 5.57 mmol) at room temperature and stirred at room temperate for 2 hours and then stirred with hydrazine monohydrate (0.272 mL, 5.57 mmol) for another 2 hours. The reaction solution was mixed with saturated aqueous sodium chloride and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated to give the crude preparation of the desired product (115% yield). extracted with ethyl acetate The extract was dried over anhydrous magnesium sulfate filtered the filtrate was concentrated to give the crude

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDCHCl (376 mg, 1.96 mmol) and Et3N (275 μL, 1.96 mmol) in anhydrous DCM (2.0 mL) and stir the resulting solution for 5 min at rt. Add 3-(3,4,5-Trimethoxy-phenyl)-propionic acid (346 mg, 1.44 mmol) and DMAP (17 mg, 0.14 mmol) and stir the resulting solution for 15 min. Add 1-(Ethoxycarbonylmethyl)piperazine (63) (224 mg, 1.30 mmol) and stir the reaction solution overnight at rt. Quench reaction solution with water, separate layers and extract aqu. layer with EtOAc (3 times). Filtrate the combined organic layer through a short pad of silica gel and remove solvent. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 9+1) to obtain {4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl ester (66) (426 mg, 83%) as a colorless oil. 1H NMR (400 MHz, CDCl3): 1.26 (t, 3H, J=7.1 Hz); 2.45-2.70 (br.m, 6H); 2.89 (t, 2 H, J=7.7 Hz); 3.26 (br.s, 2H); 3.43-3.56 (br.m, 2H); 3.61-3.76 (br.m, 2H); 3.80 (s, 3H); 3.83 (s, 6H); 4.18 (q, 2H, J=7.1 Hz); 6.41 (s, 2H). (The following reaction Quench reaction solution with water separate layers extract aqu Filtrate the combined organic layer through a short pad of silica gel and remove solvent Purify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 9+1)