Phosphoric Acid → (3-[4-(Tert-butoxycarbonyl)piperazin-1-YL]phenyl)boronic acid

HRID 1839140Notes

Reaction equation

HRID 1839140 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16](Br)[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[B:26](OC(C)C)([O:31]C(C)C)[O:27]C(C)C.[Cl-].[NH4+].OP(O)(O)=O>O1CCCC1.C1(C)C=CC=CC=1.CCCCCCC.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([B:26]([OH:31])[OH:27])[CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 1004Phosphoric AcidHCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 10882380tert-Butyl 4-(3-bromophenyl)piperazine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 22392008(3-[4-(Tert-butoxycarbonyl)piperazin-1-YL]phenyl)boronic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8900HeptaneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To the 4-tert-Butyloxycarbonyl-1-(3-bromophenyl)piperazine from Step 1 (118.30 g, 346.9 mmol) in tetrahydrofuran/toluene (1/1, 1.5 L) at −78° C. under nitrogen was added n-butyllithium (2.5M, 160 mL, 398.9 mmol) dropwise and the resulting reaction mixture 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 saturated ammonium chloride (400 mL), water (100 mL) and 1 equivalent of H3PO4 (20 mL) were added and the mixture was 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). The mixture was slowly diluted with heptane (800 mL) and the resulting suspension was stirred overnight. The suspension was filtered, the solid was washed with heptane and dried to afford the title boronic acid.

Workup

  1. customthe resulting reaction mixture
  2. temperaturethe reaction was warmed to 0° C.
  3. stirringstirred for 2 hours
  4. stirringthe mixture was stirred for 15 minutes
  5. concentrationconcentrated to a volume of approximately 200 mL (at which stage the mixture
  6. customa precipitate formed)
  7. stirringthe resulting suspension was stirred overnight
  8. filtrationThe suspension was filtered
  9. washthe solid was washed with heptane
  10. customdried

Sources & evidence

ORD record
ord-9b2b28d2e6bb4c5cb315fdd03e6b6775
Source dataset
uspto-grants-2004_01
Patent number
US06677351B2

Reaction notes

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