Methanesulfonic Acid → 5-((tert-Butyldimethylsilyl)oxy)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 41513

Reaction equation

HRID 41513 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].CS(O)(=O)=O.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>C(Cl)Cl.C1COCC1>[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:25]1[CH2:26][CH2:27][CH2:28][CH2:29][O:24]1)[N:13]=[C:12]2[I:18])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 80803,4-dihydro-2H-pyranHCID 178455023HCID 178455023, compound

Product 1

HCID 666468565-((tert-Butyldimethylsilyl)oxy)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cool a solution of 5-(tert-butyldimethylsilyloxy)-3-iodo-1H-indazole (387.00 g, 1.08 mol) in DCM (2.50 L) and THF (1.00 L) to 10° C. in a 10 L jacketed reactor vessel. To the resulting mixture add methanesulfonic acid (14.0 mL, 216.02 mmol), followed by 3,4-dihydro-2H-pyran (296 mL, 3.24 mol) over 0.5 hours, observing a slight exotherm. Stir the mixture at RT for 3 hours. Cool the reaction to 10° C. and quench with saturated aqueous sodium bicarbonate (2 L). Dilute the mixture with water (2 L) and extract the aqueous layer with DCM (2 L). Wash the combined organic extracts with water (2 L) and brine. Dry the organic mixture over anhydrous sodium sulfate, filter and concentrate in vacuo. Elute the residue through a silica gel pad with eluent (0 to 10% EA/hexanes) to give the title compound. Yield: 150 g (31%). MS (ES) m/z 459 [M+1]+.

Workup

  1. temperatureCool
  2. customthe reaction to 10° C.
  3. customquench with saturated aqueous sodium bicarbonate (2 L)
  4. additionDilute the mixture with water (2 L)
  5. extractionextract the aqueous layer with DCM (2 L)
  6. washWash the combined organic extracts with water (2 L) and brine
  7. dry with materialDry the organic mixture over anhydrous sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. washElute the residue through a silica gel pad with eluent (0 to 10% EA/hexanes)

Sources & evidence

ORD record
ord-b63694b8851b4305b4df9b49ea3df7b7
Source dataset
uspto-grants-2013_09
Patent number
US08530665B2

Linked notes

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