Tetrahydro-4H-pyran-4-one → 4-(1-(4-fluorophenyl)-1H-indazol-5-yl)tetrahydro-2H-pyran-4-ol

HRID 218164Notes

Reaction equation

HRID 218164 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13](I)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C([Mg]Br)(C)C.[Li]CCCC.[O:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:31]4([OH:34])[CH2:32][CH2:33][O:28][CH2:29][CH2:30]4)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 592511281-(4-fluorophenyl)-5-iodo-1H-indazoleHCID 178418339ButyllithiumHCID 178418365HCID 178418365, compound

Product 1

HCID 687065944-(1-(4-fluorophenyl)-1H-indazol-5-yl)tetrahydro-2H-pyran-4-olYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(4-Fluorophenyl)-5-iodo-1H-indazole (350 mg, 1.0 mmol) was dissolved in 10 mL dry THF and treated with isopropylmagnesium bromide (1.6 mL of 1 M THF solution) and then BuLi (1.6 M in hexanes, 0.72 mmol, 1.1 mmol) at room temp. After 30 min, tetrahydro-4H-pyran-4-one (270 mg, 2.7 mmol) was added. After 2 h, the reaction was quenched with water, then 1 M HCl, and extracted 2× EtOAc. The organic layers were dried over MgSO4, filtered, concentrated, and the residue was purified using 1:1 EtOAc/hexanes to give 125 mg (39%) of 4-(1-(4-fluorophenyl)-1H-indazol-5-yl)tetrahydro-2H-pyran-4-ol as a clear oil that solidified upon standing. (M+H)+=313.

Workup

  1. customat room temp
  2. waitAfter 2 h
  3. customthe reaction was quenched with water
  4. extraction1 M HCl, and extracted 2× EtOAc
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified

Sources & evidence

ORD record
ord-37e7cad8b9af4755aba02bc45be69d47
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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