Ethyl Acetate → 3-Iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole-5-carbaldehyde

HRID 1615349Notes

Reaction equation

HRID 1615349 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7](C=O)=[CH:8][CH:9]=2)[NH:4][N:3]=1.Cl[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19].[C:22](OCC)(=[O:24])C>C(Cl)Cl.[OH-].[K+].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:22]=[O:24])[CH:9]=2)[N:4]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:3]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178519327HCID 178519327, compound

Product 1

HCID 584075833-Iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole-5-carbaldehyde

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolventHCID 14797Potassium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 3-iodo-1H-indazole-6-carbaldehyde (126.6 mg, 0.46 mmol) in CH2Cl2 (5 mL) and 50% aq. KOH (1.0 mL) was added tetrabutylammonium bromide (3.4 mg, 0.01 mmol) and the solution cooled to 0° C. (2-(Chloromethoxy)ethyl)trimethylsilane (0.10 mL, 0.56 mmol) was then added dropwise and the reaction stirred at 0° C. for 1.5 hours. The solution was then transferred to a sep. funnel containing ethyl acetate (200 mL) and the organic layer was washed with water (2×20 mL) and brine (20 mL), dried (Na2SO4) and the solvent removed in vacuo. The resulting residue was adsorbed onto silica using dichloromethane-methanol to dissolve, and evaporated to dryness. Chromatography (10 g silica SPE tube, Silicycle, 50-100% dichloromethane in hexane, 10% ethyl acetate in dichloromethane) to give 88 mg, 47%. 1H NMR: (400 MHz, CDCl3) δ 10.12 (s, 1H), 8.05 (m, 2H), 7.67 (d, J=9.2 Hz, 1H), 5.77 (s, 2H), 3.60 (m, 2H), 0.90 (m, 2H), −0.048 (s, 9H).

Workup

  1. additionwas then added dropwise
  2. washthe organic layer was washed with water (2×20 mL) and brine (20 mL)
  3. dry with materialdried (Na2SO4)
  4. customthe solvent removed in vacuo
  5. dissolutionto dissolve
  6. customevaporated to dryness
  7. customChromatography (10 g silica SPE tube, Silicycle, 50-100% dichloromethane in hexane, 10% ethyl acetate in dichloromethane) to give 88 mg, 47%

Sources & evidence

ORD record
ord-c175e002adda4cc2aaedeeae456db71d
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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