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

HRID 751262Notes

Reaction equation

HRID 751262 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 4, 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 solid sodium chloride, and remove the solvent under reduced pressure to afford an oil. Purify by normal phase flash chromatography (120 g Biotage KP-Sil 40 L: ethyl acetate for 25 min, 0-10% methanol in ethyl acetate in ramp over 15 min, then 10% methanol in ethyl acetate) to obtain the title product (1.43 g, 55%). MS ES+ m/e 230 (M+1).

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 solid sodium chloride
  6. customremove the solvent under reduced pressure
  7. customto afford an oil
  8. customPurify by normal phase flash chromatography (120 g Biotage KP-Sil 40 L
  9. wait0-10% methanol in ethyl acetate in ramp over 15 min

Sources & evidence

ORD record
ord-4cf996f7e5b44a9eb7fe8a81c6a45edb
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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