Sodium Iodide → Butyl 4-(2-hydroxy-2-methylpropyl)piperazine-1-carboxylate
Reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])(C)C)=[O:2].[CH3:14][CH2:15]N(C(C)C)C(C)C.Cl[CH2:24][C:25]([CH3:28])([OH:27])[CH3:26].[Na+].[I-]>CS(C)=O.CCOC(C)=O.CO.C(Cl)Cl>[OH:27][C:25]([CH3:28])([CH3:26])[CH2:24][N:11]1[CH2:10][CH2:9][N:8]([C:1]([O:3][CH2:4][CH2:7][CH2:14][CH3:15])=[O:2])[CH2:13][CH2:12]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 67.5 °C
Procedure
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).
Workup
- temperaturethe reaction mixture was heated at 70-75° C. over weekend
- washsuccessively washed with 10% Na2S2O5 in water, water
- dry with materiala saturated aqueous solution of sodium bicarbonate, water and brine, dried over anhydrous magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by Biotage (Snap 25 g cartridge
Sources & evidence
- ORD record
- ord-8db035aa07e641de8d8b95fdaee402a4
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08906852B2
Reaction notes
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