Sodium Hydroxide → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-[4-(methoxy)phenyl]-1-benzofuran-2-carboxamide

HRID 1012721Notes

Reaction equation

HRID 1012721 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[N:12]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C@@H:14]([NH:20][C:21]([C:23]1[O:24][C:25]3[CH:31]=[C:30](Br)[CH:29]=[CH:28][C:26]=3[CH:27]=1)=[O:22])[CH2:13]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:12]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C@@H:14]([NH:20][C:21]([C:23]1[O:24][C:25]3[CH:31]=[C:30]([C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH:29]=[CH:28][C:26]=3[CH:27]=1)=[O:22])[CH2:13]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 201262(4-Methoxyphenyl)boronic acidHCID 59341401N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzofuran-2-carboxamide

Product 1

HCID 58485555N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-[4-(methoxy)phenyl]-1-benzofuran-2-carboxamide

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 130 mg (0.86 mmol) of 4-methoxyphenylboronic 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. 160 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-6f1698509b7a4b39a36d7441e0885038
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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