Sodium Iodide → Butyl 4-(2-hydroxy-2-methylpropyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence