反应详情

温度

67.5 °C

To a stirred solution of 1-Boc-piperazine (1.00 g, 5.37 mmol) and DIPEA (1.41 ml, 8.05 mmol) in DMSO (20 ml) under nitrogen at rt was added 1-chloro-2-methyl-2-propanol (1.65 ml, 16.11 mmol) and the reaction mixture was heated at 65-70° C. overnight. NaI (161 mg, 1.07 mmol) and more 1-chloro-2-methyl-2-propanol (1.65 ml, 16.11 mmol) were added, and the reaction mixture was heated at 70-75° C. over weekend. The reaction mixture was then diluted with AcOEt, and successively washed with 10% Na2S2O5 in water, water, a saturated aqueous solution of sodium bicarbonate, water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by Biotage (Snap 25 g cartridge: MeOH/DCM: 0/100 to 5/95 over 20 CV, then 5/95 to 10/90 over 5 CV), to afford the desired product 563 (460 mg, 1.78 mmol, 33% yield) as a dark yellow oil. MS (m/z): 203.11 and 259.23 (M+H).

1. temperaturethe reaction mixture was heated at 70-75° C. over weekend
2. washsuccessively washed with 10% Na2S2O5 in water, water
3. dry with materiala saturated aqueous solution of sodium bicarbonate, water and brine, dried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by Biotage (Snap 25 g cartridge