Sodium Hydroxide → (3R)-N-[2'-(Hydroxymethyl)-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

HRID 722188Notes

Reaction equation

HRID 722188 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.Br[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C@@H:22]2[CH:27]3[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]3)[CH2:23]2)=[O:21])=[CH:15][CH:14]=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>[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C@@H:22]2[CH:27]3[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]3)[CH2:23]2)=[O:21])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 43742622-(Hydroxymethyl)phenylboronic AcidHCID 58742393(3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide

Product 1

HCID 58742401(3R)-N-[2'-(Hydroxymethyl)-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 90 mg (0.58 mmol) of 2-(hydroxymethyl)phenylboronic 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 42 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). 56 mg (39% of theory) of the title compound are obtained.

Workup

  1. temperatureis heated at 80–85° C. for 42 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)

Sources & evidence

ORD record
ord-7c93fa14db6b46c7a1f6e2cc09cd5912
Source dataset
uspto-grants-2006_11
Patent number
US07138410B2

Reaction notes

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