Hydrochloric Acid → 1-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1h-indazol-4-ol

HRID 2423073Notes

Reaction equation

HRID 2423073 reaction equation
Br[C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:14]([F:26])[CH:13]=1.[OH-:27].[K+].CC(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)C.Cl>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:26][C:14]1[CH:13]=[C:12]([N:6]2[C:7]3[CH:8]=[C:9]([CH3:11])[CH:10]=[C:2]([OH:27])[C:3]=3[CH:4]=[N:5]2)[CH:17]=[CH:16][C:15]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 592729664-Bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1h-indazole

Product 1

HCID 1360852441-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1h-indazol-4-olYield 46.6%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1H-indazole (D12) (1.97 g, 4.5 mmol) and KOH (1 g, 18 mmol) in dioxane (50 mL) and water (50 mL) was sonicated under a flow of argon for 5 minutes after which the bis(1,1-dimethylethyl)[2′,4′,6′-tris(1-methylethyl)-2-biphenylyl]phosphane (115 mg, 0.27 mmol) and Pd2 dba3 (82 mg, 0.09 mmol) were added and it was heated to reflux for 2 hours. The mixture was then cooled to room temperature, diluted with EtOAc and water and the pH was adjusted to circa 7 with 1M HCl. The phases were separated, the aqueous re-extracted with EtOAc and the combined organics were finally dried over MgSO4. The crude material (2.1 g) was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc 0 to 50% in hexane to afford 730 mg of desired compound (D13).

Workup

  1. additionwere added
  2. temperatureit was heated
  3. temperatureto reflux for 2 hours
  4. customThe phases were separated
  5. extractionthe aqueous re-extracted with EtOAc
  6. dry with materialthe combined organics were finally dried over MgSO4
  7. customThe crude material (2.1 g) was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc 0 to 50% in hexane

Sources & evidence

ORD record
ord-748edfbb075743d88dd62d374360525c
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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