2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 1-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine

HRID 216713Notes

Reaction equation

HRID 216713 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li]CCCC.C(O[B:24]1[O:28][C:27]([CH3:30])([CH3:29])[C:26]([CH3:32])([CH3:31])[O:25]1)(C)C>C1COCC1.[NH4+].[Cl-]>[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([B:24]3[O:28][C:27]([CH3:30])([CH3:29])[C:26]([CH3:32])([CH3:31])[O:25]3)=[CH:3][CH:4]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 118176751-(4-Bromophenyl)-4-methylpiperazineHCID 178418339Butyllithium

Product 1

HCID 179989051-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Procedure

To a cooled (−78° C.) solution of 1-(4-Bromo-phenyl)-4-methyl-piperazine (8.05 g, 31.54 mmol, CAS 130307-08-3) in dry THF (500 ml) are added dropwise 28 ml of a solution of n-BuLi (2.5M in hexanes, 69 mmol). After 1 h, of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (13.1 ml, 63.1 mmol) in solution in dry THF (20 ml) are introduced. After complete addition, the reaction mixture is allowed to slowly warm up to RT. The reaction mixture is then diluted with 200 ml of a saturated solution of NH4Cl and most of the THF is removed by evaporation. The residue is diluted with EtOAc and the phases are separated. The aqueous phase is re-extracted three times with EtOAc and the combined organic extracts are washed twice with de-ionized water, once with saturated brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue is purified by chromatography (silicagel, CH2Cl2/EtOH 9:1) to afford the title compound as a colorless solid, Rt=0.851 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 303 (M+1)+.

Workup

  1. additionAfter complete addition
  2. customis removed by evaporation
  3. additionThe residue is diluted with EtOAc
  4. customthe phases are separated
  5. extractionThe aqueous phase is re-extracted three times with EtOAc
  6. washthe combined organic extracts are washed twice with de-ionized water, once with saturated brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by chromatography (silicagel, CH2Cl2/EtOH 9:1)

Sources & evidence

ORD record
ord-35d49eea4f44401390691136571ed0e3
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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