Phosphoric Acid → 4-(4-BOC-Piperazino)phenylboronic acid

HRID 1744048Notes

Reaction equation

HRID 1744048 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li]CCCC.[B:26](OC(C)C)([O:31]C(C)C)[O:27]C(C)C.[NH4+].[Cl-].OP(O)(O)=O>C1COCC1.CC1C=CC=CC=1.CCCCCCC.O>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([B:26]([OH:31])[OH:27])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

9

Reactant 5

HCID 1004Phosphoric AcidHCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 11824027Tert-butyl 4-(4-bromophenyl)piperazine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 52330144-(4-BOC-Piperazino)phenylboronic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8900HeptaneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To tert-butyl 4-(4-bromophenyl)-1-piperazinecarboxylate (118.30 g, 346.9 mmol) in dry THF/MePh (1/1, 1.5 L) at −78° C. under dry nitrogen was added n-BuLi (2.5 M, 160 mL, 398.9 mmol) dropwise and the reaction was stirred at −78° C. for 20 minutes. Triisopropyl borate (96.1 mL, 416.3 mmol) was added dropwise and the reaction was warmed to 0° C. and stirred for 2 hours. Aqueous sat. NH4Cl (400 mL), water (100 mL) and 1 equivalent of H3PO4 (20 ML) were added and the mixture stirred for 15 minutes and then concentrated to a volume of approximately 200 mL (at which stage the mixture became bluish and a precipitate formed). A dropping funnel was charged with heptane (800 mL) and the solvent was added to the reaction mixture with vigorous stirring over a period of one hour and the resulting suspension was stirred overnight. The suspension was filtered, washed with heptane (2×200 mL), and dried over the weekend in vacuo to afford 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid.

Workup

  1. temperaturethe reaction was warmed to 0° C.
  2. stirringstirred for 2 hours
  3. stirringthe mixture stirred for 15 minutes
  4. concentrationconcentrated to a volume of approximately 200 mL (at which stage the mixture
  5. customa precipitate formed)
  6. additionthe solvent was added to the reaction mixture
  7. stirringwith vigorous stirring over a period of one hour
  8. stirringthe resulting suspension was stirred overnight
  9. filtrationThe suspension was filtered
  10. washwashed with heptane (2×200 mL)
  11. customdried over the weekend in vacuo

Sources & evidence

ORD record
ord-613d711bae114bdabe3d1efc01a9d0e6
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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