(3,5-dichlorophenyl)methyl piperazine-1-carboxylate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-Dichlorobenzyl piperazine-1-carboxylate (Example 26, step 2) (3.466 mg, 11.99 mmol), potassium carbonate (4.97 g, 36 mmol) and triethlyamine (5.01 ml, 36 mmol) were suspended in MeCN (60 ml). tert-Butyl(2-bromoethyl)carbamate (3.49 g, 15.58 mmol) was added and the reaction mixture was refluxed for 18 hrs at 80° C. A further portion of tert-butyl(2-bromoethyl)carbamate (1.05 g, 4.69 mmol) was added and heating continued at 80° C. for 3 hrs. After cooling to RT, the reaction mixture was diluted with EtOAc and filtered. The organic portion was evaporated under reduced pressure. The crude product was solubilised in EtOAc and washed with 2M NaOH. The organic portion was dried over MgSO4 (anh) filtered and evaporated under reduced pressure. Purification by chromatography on silica using a gradient solvent system of DCM to 10% MeOH with ammonia in DCM afforded product fractions that were concentrated to give the title compound; heating After cooling to RT filtered The organic portion was evaporated under reduced pressure washed with 2M NaOH The organic portion was dried over MgSO4 (anh) filtered evaporated under reduced pressure Purification by chromatography on silica using a gradient solvent system of DCM to 10% MeOH with ammonia in DCM afforded product fractions that were concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-butyl methyl(3-oxopropyl)carbamate (step 3) (1.528 g, 8.16 mmol) was solubilised in DCM (50 ml) and added to 3,5-dichlorobenzyl piperazine-1-carboxylate (step 2) (3.09 g, 9.82 mmol). The resulting mixture was treated with acetic acid (56 μl, 0.982 mmol) and after stirring for 1 hr at RT, sodium triacetoxyborohydride (4.16 g, 19.64 mmol) was added. The reaction mixture was stirred at RT overnight and then quenched by addition of 2M NaOH (aq.). The aqueous layer was basified to pH 14 with conc NaOH solution. The organic layer was separated and the aqueous layer was extracted with more DCM. The organic portions were combined, dried over MgSO4 (anh), filtered and evaporated under reduced pressure, yielding a yellow oil. The crude product was purified by chromatography on silica eluting with 0-10% MeOH (with ammonia) in DCM to afford the title compound; The reaction mixture was stirred at RT overnight quenched by addition of 2M NaOH (aq.) The organic layer was separated the aqueous layer was extracted with more DCM dried over MgSO4 (anh) filtered evaporated under reduced pressure yielding a yellow oil The crude product was purified by chromatography on silica eluting with 0-10% MeOH (with ammonia) in DCM