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

HRID 2221151Notes

Reaction equation

HRID 2221151 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-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 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 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/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 40L
  9. wait0-10% methanol in ethyl acetate in ramp over 15 min

Sources & evidence

ORD record
ord-9fcec20d094c4939b3230a1da8244f64
Source dataset
uspto-grants-2008_05
Patent number
US07368445B2

Reaction notes

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