Hexane → (1-{[2-(Trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acid

HRID 1776817Notes

Reaction equation

HRID 1776817 reaction equation
CCCCCC.[Li]CCCC.[CH3:12][Si:13]([CH3:28])([CH3:27])[CH2:14][CH2:15][O:16][CH2:17][N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH:20]=[CH:19]1.[B:29](OC(C)C)([O:34]C(C)C)[O:30]C(C)C>C1COCC1>[CH3:12][Si:13]([CH3:28])([CH3:27])[CH2:14][CH2:15][O:16][CH2:17][N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH:20]=[C:19]1[B:29]([OH:34])[OH:30]

Participants

6

Reactant 4

HCID 8058HexaneHCID 21531Triisopropyl borateHCID 584313511-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 68111616(1-{[2-(Trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acidYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

A hexane solution of n-BuLi (60 mL, 150.97 mmol) was added slowly to a solution of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (25.0 g, 100.65 mmol) in dry THF (200 mL) at −70° C. under N2 protection. The mixture was stirred at −45° C. for 2 hour. After (i-PrO)3B (30.29 g, 161.03 mmol) was added, the mixture was stirred overnight warming to RT. Then the reaction mixture was quenched with 1M aqueous HCl and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4, filtered and the solvent was concentrated in vacuo under reduced pressure. The crude product was purified using column chromatography (petroleum ether:EtOAc=5:1) to provide the product of (1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acid (14.4 g, yield: 49%). 1H-NMR (CDCl3, 400 MHz) δ 8.49 (dd, J=4.8 Hz, 1.6 Hz, 1H), 8.07 (dd, J=8.0 Hz, 1.6 Hz, 1H), 7.21 (dd, J=8.0 Hz, 4.8 Hz, 1H), 6.92 (s, 1H), 6.02 (s, 2H), 3.74 (t, J=8.4 Hz, 2H), 1.08 (t, J=8.4 Hz, 2H), 0.04 (s, 9H). MS (M+H)+: 293.

Workup

  1. stirringthe mixture was stirred overnight
  2. temperaturewarming to RT
  3. customThen the reaction mixture was quenched with 1M aqueous HCl
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe solvent was concentrated in vacuo under reduced pressure
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-c2f99497fc88480f994a9f30c4eb5df4
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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