Sodium Hydroxide → (3R)-N-[4'-(4-Morpholinyl)-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

HRID 722189Notes

Reaction equation

HRID 722189 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Br[C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([C@@H:26]2[CH:31]3[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]3)[CH2:27]2)=[O:25])=[CH:19][CH:18]=1.[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:4]1([C:7]2[CH:12]=[CH:11][C:10]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([C@@H:26]4[CH:31]5[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]5)[CH2:27]4)=[O:25])=[CH:19][CH:18]=3)=[CH:9][CH:8]=2)[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 2795359(4-(Morpholin-4-yl)phenyl)boronic acidHCID 58742393(3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide

Product 1

HCID 58742409(3R)-N-[4'-(4-Morpholinyl)-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 120 mg (0.58 mmol) of 4-morpholinophenylboronic acid, 120 mg (0.39 mmol) of (3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide, 1.16 ml (1.16 mmol) of 1N sodium hydroxide solution, 30 mg (0.04 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride and 1 ml of DMF is heated at 80–85° C. for 40 h. The solvent is removed under reduced pressure. The crude product is purified by chromatography on silica gel 60 (mobile phase: dichloromethane→dichloromethane/methanol/ammonia 80:20:2). The solvent is stripped off under reduced pressure, and final residues of solvent are removed under high vacuum. 100 mg (66% of theory) of the title compound are obtained.

Workup

  1. temperatureis heated at 80–85° C. for 40 h
  2. customThe solvent is removed under reduced pressure
  3. customThe crude product is purified by chromatography on silica gel 60 (mobile phase: dichloromethane→dichloromethane/methanol/ammonia 80:20:2)
  4. customare removed under high vacuum

Sources & evidence

ORD record
ord-01c57fd4b2604815a01c886714ba88cc
Source dataset
uspto-grants-2006_11
Patent number
US07138410B2

Reaction notes

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