Potassium Phosphate, Tribasic → 3-(3-fluoro-4-hydroxyphenyl)-5-nitro-1-trityl-1H-indazole

HRID 1038137Notes

Reaction equation

HRID 1038137 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[N:4]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:3]=1.[F:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][C:39]=1[OH:40].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:33][C:34]1[CH:35]=[C:36]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=3)[N:4]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:3]=2)[CH:37]=[CH:38][C:39]=1[OH:40]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 23005361(3-Fluoro-4-hydroxyphenyl)boronic acidHCID 589464433-bromo-5-nitro-1-trityl-1H-indazole

Product 1

HCID 1363872103-(3-fluoro-4-hydroxyphenyl)-5-nitro-1-trityl-1H-indazole

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
75 °C

Procedure

A suspension of 3-bromo-5-nitro-1-trityl-1H-indazole 1AJ (10.0 g, 20.68 mmol), 3-fluoro-4-hydroxyphenylboronic acid 2AW (3.55 g, 22.78 mmol), Pd(dppf)Cl2 (1.6 g, 1.96 mmol) and K3PO4 (10.6 g, 4.99 mmol) in 200 mL of dioxane/H2O (4/1) was heated to 75° C. for overnight. After removal of most of the solvent, the black residue was diluted with EtOAc (250 mL) and H2O (60 mL). The resulting mixture was filtered through a pad of Celite. Additional 150 mL of EtOAc was used to wash the Celite cake. The filtrates were combined. The aqueous layer was separated and the organic layer was washed with brine, dried (MgSO4) and concentrated to give a green solid, which was recrystallized from CH2Cl2/hexane to give 3-(3-fluoro-4-hydroxyphenyl)-5-nitro-1-trityl-1H-indazole 3AW (8.1 g).

Workup

  1. customAfter removal of most of the solvent
  2. additionthe black residue was diluted with EtOAc (250 mL) and H2O (60 mL)
  3. filtrationThe resulting mixture was filtered through a pad of Celite
  4. washto wash the Celite cake
  5. customThe aqueous layer was separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customto give a green solid, which
  10. customwas recrystallized from CH2Cl2/hexane

Sources & evidence

ORD record
ord-c8a738d0ee364e4ba4c656f8f710cefe
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

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