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

HRID 1038136Notes

Reaction equation

HRID 1038136 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:39]=[CH:38][C:37](B(O)O)=[CH:36][C:35]=1[CH2:43][OH:44].[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:39]=[CH:38][C:37]([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:36][C:35]=1[CH2:43][OH:44]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 218655884-Fluoro-3-(hydroxymethyl)benzeneboronic acidHCID 589464433-bromo-5-nitro-1-trityl-1H-indazole

Product 1

HCID 689642193-(4-fluoro-3-hydroxymethylphenyl)-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
80 °C

Procedure

A suspension of 3-bromo-5-nitro-1-trityl-1H-indazole 1 (6 g, 12.41 mmol), 4-fluoro-3-hydroxymethylphenylboronic acid 10AV (2 g, 12.87 mmol), Pd(dppf)Cl2 (800 mg, 0.98 mmol) and K3PO4 (6 g, 28.30 mmol) in 124 mL of dioxane/H2O (25:6) was heated to 80° 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 crude 3-(4-fluoro-3-hydroxymethylphenyl)-5-nitro-1-trityl-1H-indazole 11AV (8.2 g) as a greenish yellow solid.

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

Sources & evidence

ORD record
ord-4be6f1cbf11b45cbb6cf329ee40e6899
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

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