Dibutyl sulfide → (+/-)-Ethyl 3-(4-ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoate

HRID 2099754Notes

Reaction equation

HRID 2099754 reaction equation
[CH2:1](SCCCC)[CH2:2]CC.[N:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Li].[CH3:17][C:18]1[C:26]2[C:22](=[CH:23][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:25]=2)[CH:21]=[C:20]([CH2:35][CH:36]=[CH:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:19]=1>CCOCC>[CH2:1]([C:13]1[CH:14]=[CH:15][N:10]=[C:11]([CH:36]([CH2:35][C:20]2[CH:19]=[C:18]([CH3:17])[C:26]3[C:22](=[CH:23][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:33])[CH3:34])[N:25]=3)[CH:21]=2)[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:12]=1)[CH3:2]

Participants

5

Reactant 3

HCID 11002Dibutyl sulfideHCID 69069206Ethyl 4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)but-2-enoateHCID 178506720HCID 178506720, compound

Product 1

HCID 57794570(+/-)-Ethyl 3-(4-ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoateYield 44%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 50-mL oven-dried flask was added di-n-butylsulfide (244 mg, 1.665 mmol, 4.4 equiv) and cuprous iodide (159 mg, 0.832 mmol, 2.2 equiv) under nitrogen. Anhydrous ether (1.2 mL) was added and the suspension was cooled to 0° C. before the solution of 2-pyridinyl lithium was added via canuula. A yellowish brown precipitate was formed. After stirring at 0° C. for 20 min, the cooling bath was removed and ethyl 4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)but-2-enoate (141.7 mg, 0.378 mmol, 1.0 equiv.) in anhydrous ether (1.2 mL) was added via syringe. The solution was stirred at room temperature for 1 h. The reaction mixture was then partitioned between an aqueous ammonium hydroxide/ammonium chloride solution and ethyl acetate (upon shaking, the solids gradually dissolved to a give blue aqueous solution). The layers were separated and the organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo. Flash column chromatography (5% methanol in methylene chloride) afforded the desired product (80 mg, 44%) which was carried on without farther purification. MS (ESI) 482 (MH)+.

Workup

  1. customTo a 50-mL oven-dried flask
  2. additionwas added via canuula
  3. customA yellowish brown precipitate was formed
  4. customthe cooling bath was removed
  5. stirringThe solution was stirred at room temperature for 1 h
  6. customThe reaction mixture was then partitioned between an aqueous ammonium hydroxide/ammonium chloride solution and ethyl acetate (
  7. stirringupon shaking
  8. dissolutionthe solids gradually dissolved to a give blue aqueous solution)
  9. customThe layers were separated
  10. washthe organic layer was washed with water, brine
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1cd2ae38c71e4127a4e4d8968a47d2eb
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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