Triisopropyl borate → (2-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid

HRID 1787576Notes

Reaction equation

HRID 1787576 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[N:5][N:4]2[CH2:13][CH2:14][CH2:15][C:3]=12.[B:16](OC(C)C)([O:21]C(C)C)[O:17]C(C)C.C([Li])CCC>O1CCCC1>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:6]1[C:2]([B:16]([OH:21])[OH:17])=[C:3]2[CH2:15][CH2:14][CH2:13][N:4]2[N:5]=1

Participants

5

Reactant 3

HCID 21531Triisopropyl borateHCID 597100253-bromo-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoleHCID 178418339Butyllithium

Product 1

HCID 59710031(2-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acidYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Place tetrahydrofuran (60.0 mL) in a 100 mL round-bottom flask equipped with a temperature probe, a magnetic stirrer, and a septum and put under a nitrogen atmosphere. Add 3-bromo-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (Preparation 3, Part D; 3.00 g, 11.4 mmol) and triisopropyl borate (6.80 mL, 29.5 mmol). Cool the mixture to −78° C. using a dry ice/acetone bath. Add 1.41M n-butyllithium in hexanes (19.3 mL, 27.3 mmol) dropwise via a syringe pump over 10 min keeping the temperature below −40° C. Remove the dry ice/acetone bath and allow the reaction mixture to warm to room temperature. Add saturated aqueous ammonium chloride (20 mL) and extract with chloroform (2×150 mL). Combine the organic layers, dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure to afford an oil. Purify by normal phase flash chromatography (120 g Biotage KP-Sil 40L: ethyl acetate for 25 min, 0-10% methanol in ethyl acetate in ramp over 15 min, then 10% methanol in ethyl acetate) to obtain 1.43 g (55%) of the title product. MS (ES) m/z=230 (M+H).

Workup

  1. customthe temperature below −40° C
  2. customRemove the dry ice/acetone bath
  3. temperatureto warm to room temperature
  4. extractionAdd saturated aqueous ammonium chloride (20 mL) and extract with chloroform (2×150 mL)
  5. dry with materialCombine the organic layers, dry over anhydrous sodium sulfate
  6. customremove the solvent under reduced pressure
  7. customto afford an oil
  8. customPurify by normal phase flash chromatography (120 g Biotage KP-Sil 40L
  9. wait0-10% methanol in ethyl acetate in ramp over 15 min

Sources & evidence

ORD record
ord-6b50a2bbd3e14c1a869752d9e1f164f9
Source dataset
uspto-grants-2009_03
Patent number
US07511056B2

Reaction notes

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