p-Toluenesulfonic acid → 6-Bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbaldehyde

HRID 340057Notes

Reaction equation

HRID 340057 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>C(Cl)Cl.C1CCCCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[N:7][N:8]2[CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29][O:24]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 178520021HCID 178520021, compound

Product 1

HCID 866762676-Bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbaldehydeYield 73%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-bromo-1H-indazole-3-carbaldehyde (13.97 g, 61.9 mmol) in DCM (150 mL) was added p-TsOH (2.36 g, 12.4 mmol) and the mixture was cooled to 0° C. 3,4-Dihydro-2H-pyran (8.47 mL, 92.8 mmol) was added dropwise to the solution and the reaction was stirred at room temperature overnight. The reaction mixture was diluted with DCM (200 mL) and washed with a solution of saturated aqueous sodium hydrogen carbonate (500 mL). The aqueous layer was re-extracted with DCM (500 mL) and the combined organic layers were washed with brine (2×1 L), dried over MgSO4 and concentrated in vacuo to yield a black oil. The crude material was refluxed in cyclohexane (20 mL) and filtered while hot. The filtrate was concentrated in vacuo and the residue was stirred in heptane for 48 hours. The resulting solid was collected by filtration to give the title compound (13.87 g) in a 73% yield.

Workup

  1. washwashed with a solution of saturated aqueous sodium hydrogen carbonate (500 mL)
  2. extractionThe aqueous layer was re-extracted with DCM (500 mL)
  3. washthe combined organic layers were washed with brine (2×1 L)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto yield a black oil
  7. filtrationfiltered while hot
  8. concentrationThe filtrate was concentrated in vacuo
  9. stirringthe residue was stirred in heptane for 48 hours
  10. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-ad743c1a52de4f77a6491db583feeda7
Source dataset
uspto-grants-2014_11
Patent number
US08895544B2

Reaction notes

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