Phosphoric Acid → 4-(4-{[(Triisopropylsilyl)oxy]carbonyl}-1-piperazinyl)phenylboronic acid

HRID 1744063Notes

Reaction equation

HRID 1744063 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][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([O:30][B:31](OC(C)C)[O:32]C(C)C)(C)C.P(=O)(O)(O)O>C1(C)C=CC=CC=1.O1CCCC1>[CH:18]([Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([B:31]([OH:32])[OH:30])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 1004Phosphoric AcidHCID 21531Triisopropyl borateHCID 22235752Triisopropylsilyl 4-(4-bromophenyl)-1-piperazinecarboxylate

Product 1

HCID 222360254-(4-{[(Triisopropylsilyl)oxy]carbonyl}-1-piperazinyl)phenylboronic acid

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of triisopropylsilyl 4-(4-bromophenyl)-1-piperazinecarboxylate (4.5 g, 10.2 mmoles) in toluene (17 mL) and tetrahydrofuran (17 mL) was degassed by bubbling nitrogen at room temperature via a fritted gas dispenser for 10 minutes and then cooled to −78° C. for the addition of butyllithium (4.9 mL as a 2.5 M solution in hexanes, 12.3 mmoles). The solution turned yellow and after 30 minutes, triisopropylborate (3 mL, 13.3 mmoles) was added and the solution was warmed to 0° C. over 2.5 h prior to quenching with sat. aq. ammonium chloride (22 mL). To the flask was added 0.825 mL of phosphoric acid (14.8 M, 12.3 mmoles). The solution was stirred for 30 minutes. The phases were separated and the organic phase was dried over sodium sulfate. Right after filtering off the drying agent, the organic phase was washed with wet tetrahydrofuran (approx 2% water). The solution was concentrated to approx 15 mL. While concentrating, three 0.5 mL-portions of water were added to prevent boroxine formation. At this point, hexane was added and the resulting precipitate was filtered to yield 4-(4-{[(triisopropylsilyl)oxy]carbonyl}-1-piperazinyl)phenylboronic acid.

Workup

  1. customby bubbling nitrogen at room temperature via a fritted gas dispenser for 10 minutes
  2. temperaturethe solution was warmed to 0° C. over 2.5 h
  3. customto quenching with sat. aq. ammonium chloride (22 mL)
  4. customThe phases were separated
  5. dry with materialthe organic phase was dried over sodium sulfate
  6. filtrationRight after filtering off the drying agent
  7. washthe organic phase was washed with wet tetrahydrofuran (approx 2% water)
  8. concentrationThe solution was concentrated to approx 15 mL
  9. concentrationWhile concentrating
  10. additionthree 0.5 mL-portions of water were added
  11. additionAt this point, hexane was added
  12. filtrationthe resulting precipitate was filtered

Sources & evidence

ORD record
ord-d5e3906d5d3c4b17bafc9e4cbd4adba6
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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