Hydrochloric Acid → 1-tert-butyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 473340Notes

Reaction equation

HRID 473340 reaction equation
Br[C:2]1[C:3](C(C)(C)C)=[N:4][NH:5][CH:6]=1.[Li]C[CH2:13][CH2:14][CH3:15].[B:16]([OH:19])(O)[OH:17].C([CH2:23][C:24]([C:27](O)([CH3:29])[CH3:28])([CH3:26])O)(C)C.Cl.[CH2:32]1COCC1>O>[CH3:32][C:14]([N:5]1[CH:6]=[C:2]([B:16]2[O:19][C:27]([CH3:28])([CH3:29])[C:24]([CH3:23])([CH3:26])[O:17]2)[CH:3]=[N:4]1)([CH3:13])[CH3:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 131731157iso-Propyl pinacol borateHCID 178418339ButyllithiumHCID 178441971HCID 178441971, compound

Product 1

HCID 532171091-tert-butyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 20 L four-neck bottle, 4-bromo-(tert-butyl)pyrazole (1.15 kg, 5.66 mol) and THF (9.2 L) were added, then the mixture was cooled to between −78° C. and −85° C. and treated with nBuLi (6.23 mol) dropwise at that temperature. After addition the solution was stirred at the same temperature for 1 h and isopropyl pinacol borate (1.47 kg, 7.92 mol) was added dropwise. The reaction was complete after stirring for ˜3 h (starting material<1.0% a/a by GC) then water (2.3 L) was added to quench the reaction; and the pH adjusted to 8-9 by addition of 3.45 kg 1M HCl. The aqueous phase was extracted with TBME (3.45 L×2), and the combined organic phase washed with 5% NaCl (3.45 L×2) and water (3.45 L) in sequence. The organic phase was evaporated to give the crude product. After subsequent recrystallization from heptanes the pure product was obtained as a white solid (GC purity 99.7% a/a) in a 63.5% th overall yield. (Two 20 L reactions were run, then combined in the heptane recrystallization).

Workup

  1. temperaturethe mixture was cooled to between −78° C. and −85° C.
  2. additionAfter addition the solution
  3. stirringafter stirring for ˜3 h (starting material<1.0% a/a by GC)
  4. customto quench
  5. customthe reaction
  6. extractionThe aqueous phase was extracted with TBME (3.45 L×2)
  7. washthe combined organic phase washed with 5% NaCl (3.45 L×2) and water (3.45 L) in sequence
  8. customThe organic phase was evaporated

Sources & evidence

ORD record
ord-22f69ef022da4b26bf6815c4dfdf9402
Source dataset
uspto-grants-2014_01
Patent number
US08633319B2

Reaction notes

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