3,4-dihydro-2H-pyran → 4-Bromomethyl-1-(tetrahydro-pyran-2-yl)-1H-indazole

HRID 1952550Notes

Reaction equation

HRID 1952550 reaction equation
[Br:1][CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[Br:1][CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][N:7]2[CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][O:12]1

Participants

6

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 22661308HCID 22661308, compound

Product 1

HCID 226612154-Bromomethyl-1-(tetrahydro-pyran-2-yl)-1H-indazoleYield 86.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-bromomethyl-1H-indazole (2.0 g, 9.476 mmol), 3,4-dihyro-2H-pyran (4.0 mL, 43.84 mmol), p-toluenesulfonic acid monohydrate (2.0 g, 10.51 mmol) and anhydrous THF (20 mL) was heated at 60° C. for 1 h. The reaction mixture was cooled, added to aqueous saturated sodium carbonate solution (50 mL) and extracted with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (20% EtOAc in hexanes) to give 4-bromomethyl-1-(tetrahydro-pyran-2-yl)-1H-indazole (2.43 g, 86.9%) as an off white solid. MS m/e 296.2 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with ethyl acetate (200 mL)
  3. washThe organic layer was washed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude compound was purified by flash chromatography (20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f9f9cccada9e4aae8b2b4b6a73e734e3
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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