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

HRID 2221146Notes

Reaction equation

HRID 2221146 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[N:8]=2)=[N:5][N:4]2[CH2:14][CH2:15][CH2:16][C:3]=12.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C.C([Li])CCC>O1CCCC1>[CH3:13][C:9]1[N:8]=[C:7]([C:6]2[C:2]([B:17]([OH:22])[OH:18])=[C:3]3[CH2:16][CH2:15][CH2:14][N:4]3[N:5]=2)[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 21531Triisopropyl borateHCID 99002873-bromo-2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoleHCID 178418339Butyllithium

Product 1

HCID 247701172-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acidYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Place tetrahydrofuran (28.0 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-[6-methyl-(pyridin-2-yl)]-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (1.44 g, 5.18 mmol) and triisopropyl borate (3.10 mL, 13.5 mmol). Cool the mixture to −78° C. using a dry ice/acetone bath. Add 1.4M n-butyllithium in hexanes (8.80 mL, 12.4 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 (10 mL) and extract with chloroform (2×100 mL). Combine the organic layers, dry over solid sodium chloride, and remove the solvent under reduced pressure to afford an oil. Purify the oil by normal phase flash chromatography (120 g Biotage KP-Sil 40L: 100% ethyl acetate in hexanes for 25 min, 0-10% methanol in ethyl acetate in ramp over 15 min, then 10% methanol in ethyl acetate) to yield 910 mg (73%) of the title compound. MS ES+ m/e 244 (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 (10 mL) and extract with chloroform (2×100 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 the oil 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-6baef202c3464f19a65d05ae45811747
Source dataset
uspto-grants-2008_05
Patent number
US07368445B2

Reaction notes

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