Water → 5-((tert-Butyldimethylsilyl)oxy)-3-iodo-1-methyl-1H-indazole

HRID 246614Notes

Reaction equation

HRID 246614 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[I:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O([C:21](C)(C)C)[K].CI.O>C1COCC1>[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:21])[N:13]=[C:12]2[I:18])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 178418922HCID 178418922, compoundHCID 178455023HCID 178455023, compound

Product 1

HCID 712798665-((tert-Butyldimethylsilyl)oxy)-3-iodo-1-methyl-1H-indazoleYield 80.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(tert-butyldimethylsilyloxy)-3-iodo-1H-indazole (3 g, 8.0 mmol) in THF (25 mL) was added KO-tBu (1.28 g, 11.2 mmol) at 0° C. followed by addition of MeI (1.58 g, 11.2 mmol), after the addition, the reaction mixture was warmed to room temperature and stirred for 4 hours, then H2O (25 mL) was added to the mixture and product extracted with EtOAc (100 mL). The organic layer was washed with H2O (100 mL), brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure, the residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with petroleum ether/EtOAc=5:1) to give 5-(tert-butyldimethylsilyloxy)-3-iodo-1-methyl-1H-indazole (2.5 g, 80.3%) as a white solid. (M+H)+=389; 1H NMR (300 MHz, CDCl3), δ 7.22-7.19 (m, 1H), 7.03-7.01 (m, 1H), 6.80 (s, 1H), 4.05 (s, 3H), 1.01 (s, 9H), 0.23 (s, 6H).

Workup

  1. additionafter the addition
  2. extractionextracted with EtOAc (100 mL)
  3. washThe organic layer was washed with H2O (100 mL), brine (100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customthe residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with petroleum ether/EtOAc=5:1)

Sources & evidence

ORD record
ord-a51d39fae6224988a1ab16c25e5e8671
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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