2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 7-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine

HRID 633552Notes

Reaction equation

HRID 633552 reaction equation
I[C:2]1[C:10]2[C:5](=[C:6]([O:11][CH3:12])[N:7]=[CH:8][CH:9]=2)[N:4]([CH3:13])[CH:3]=1.C([Li])CCC.C(O[B:23]1[O:27][C:26]([CH3:29])([CH3:28])[C:25]([CH3:31])([CH3:30])[O:24]1)(C)C>>[CH3:12][O:11][C:6]1[N:7]=[CH:8][CH:9]=[C:10]2[C:2]([B:23]3[O:27][C:26]([CH3:29])([CH3:28])[C:25]([CH3:31])([CH3:30])[O:24]3)=[CH:3][N:4]([CH3:13])[C:5]=12

Participants

4

Reactant 3

HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 903878133-iodo-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridineHCID 178418339Butyllithium

Product 1

HCID 903879807-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridineYield 70.7%

Conditions

Temperature
-78 °C

Procedure

3-Iodo-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridine (3.89 g, 13.50 mmol) was flow purged with nitrogen for 30 minutes, then treated with tetrahydrofuran (135 mL). The reaction mixture was cooled to −78° C. Butyllithium (5.40 mL, 13.50 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 30 minutes. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.75 mL, 13.50 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 2.5 hours. The reaction mixture was poured onto water and extracted twice with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 100% heptane to 30% ethyl acetate/heptane) to provide the title compound (2.75 g, 70% yield).

Workup

  1. custompurged with nitrogen for 30 minutes
  2. additiontreated with tetrahydrofuran (135 mL)
  3. stirringThe reaction mixture was stirred at −78° C. for 2.5 hours
  4. additionThe reaction mixture was poured onto water
  5. extractionextracted twice with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (silica gel, 100% heptane to 30% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-199a9f5da8a441069d20bb34a2cfd446
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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