Sodium Hydroxide → HCID 58485542, compound

HRID 1012723Notes

Reaction equation

HRID 1012723 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[N:11]12[CH2:18][CH2:17][CH:14]([CH2:15][CH2:16]1)[C@@H:13]([NH:19][C:20]([C:22]1[O:23][C:24]3[CH:30]=[C:29](Br)[CH:28]=[CH:27][C:25]=3[CH:26]=1)=[O:21])[CH2:12]2.[OH-].[Na+]>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].CN(C=O)C>[N:11]12[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18]1)[C@@H:13]([NH:19][C:20]([C:22]1[O:23][C:24]3[CH:30]=[C:29]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH:28]=[CH:27][C:25]=3[CH:26]=1)=[O:21])[CH2:12]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 2856454-Fluorophenylboronic acidHCID 59341401N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzofuran-2-carboxamide

Product 1

HCID 58485542HCID 58485542, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
82.5 °C

Procedure

A mixture of 120 mg (0.86 mmol) of 4-fluorophenylboronic acid, 200 mg (0.57 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzofuran-2-carboxamide (Example 2A), 1.72 ml (1.72 mmol) of 1N sodium hydroxide solution, 40 mg (0.06 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride and 2 ml of DMF is heated at 80-85° C. for 18 h. The solvent is removed under reduced pressure. The crude product is purified on silica gel 60 (Merck, Darmstadt; eluent: dichloromethane, dichloromethane/methanol 20:1, dichloromethane/methanol/ammonia 80:20:2). The solvent is removed under reduced pressure. Finally, the last residues of solvent are removed under high vacuum. 155 mg (68% of theory) of the title compound are isolated.

Workup

  1. customThe solvent is removed under reduced pressure
  2. customThe crude product is purified on silica gel 60 (Merck, Darmstadt; eluent: dichloromethane, dichloromethane/methanol 20:1, dichloromethane/methanol/ammonia 80:20:2)
  3. customThe solvent is removed under reduced pressure
  4. customFinally, the last residues of solvent are removed under high vacuum

Sources & evidence

ORD record
ord-5ce41fc1749249bb8310455ad3eccdfd
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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