tert-butyl 2-(4-methylpiperazin-1-yl)acetate

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: To a suspension of 1-methylpiperazine dihydrochloride (8.5 g, 49.2 mmol) and triethylamine (22.8 mL, 164.0 mmol) in THF (150 mL) was added tert-butyl 2-bromoacetate (8.0 g, 41.0 mmol). The mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with EtOAc (200 mL) and H2O (100 mL). The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness. The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2) to afford the sub-title compound (6.0 g, 69%). The organic phase was washed with brine dried (MgSO4) filtered concentrated to dryness The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2)

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

Procedure: tert-Butyl(4-methylpiperazin-1-yl)acetate (3.50 g, 16.3 mmol) was suspended in 4N hydrogen chloride/1,4-dioxane (35 mL) solution, trifluoroacetic acid (60 mL) was added to give a solution, and the solution was stirred at room temperature for 4 hr. The reaction mixture was concentrated under reduced pressure, 4N hydrogen chloride/ethyl acetate (30 mL) was added to the obtained oily residue to give a suspension, and the suspension was stirred at room temperature for 2 hr. The obtained precipitate was collected by filtration, washed with ethyl acetate and diisopropyl ether on filter paper, and dried to give the title compound (3.33 g, 88%) as a colorless powder. The compound was used for the next reaction without further purification operation. was added to give a solution The reaction mixture was concentrated under reduced pressure, 4N hydrogen chloride/ethyl acetate (30 mL) was added to the obtained oily residue to give a suspension the suspension was stirred at room temperature for 2 hr The obtained precipitate was collected by filtration washed with ethyl acetate and diisopropyl ether on filter paper dried

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of tert-butyl chloroacetate (3.49 g, 34.9 mmol) and potassium carbonate (5.50 g, 39.8 mmol) in acetonitrile (300 mL) was added dropwise 1-methylpiperazine (5.00 g, 33.2 mmol), and the mixture was stirred with heating at 50° C. for 16 hr. The reaction mixture was cooled to room temperature, the insoluble material was filtered off, and the filtrate was concentrated. Water (150 mL) was added to the obtained residue, and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (150 mL) and saturated brine (150 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated to give the title compound (5.63 g, 79%) as a pale-yellow oil. The compound was used for the next reaction without further purification operation. The reaction mixture was cooled to room temperature the insoluble material was filtered off the filtrate was concentrated Water (150 mL) was added to the obtained residue the mixture was extracted with ethyl acetate (300 mL) The organic layer was washed with water (150 mL) and saturated brine (150 mL) dried over anhydrous sodium sulfate The insoluble material was filtered off the filtrate was concentrated