Sodium Hydroxide → HCID 21883467, compound

HRID 722186Notes

Reaction equation

HRID 722186 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[OH-].[Na+].[ClH:14].[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[CH:17]([CH2:23][C:24]([NH:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29](Br)[CH:28]=1)=[O:25])[CH2:16]2>CN(C=O)C.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]>[ClH:14].[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[CH:17]([CH2:23][C:24]([NH:26][C:27]1[CH:28]=[C:29]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[CH2:2][OH:1])[CH:30]=[CH:31][CH:32]=1)=[O:25])[CH2:16]2

Participants

6

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 43742622-(Hydroxymethyl)phenylboronic Acid2×HCID 218834582-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(3-bromophenyl)acetamide Hydrochloride

Product 1

HCID 21883467HCID 21883467, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

48.1 mg (0.32 mmol) of 2-(hydroxymethyl)phenylboronic acid, 0.95 ml (0.95 mmol) of 1M sodium hydroxide solution and 51.7 mg (0.06 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride are added to a solution of 150 mg (0.32 mmol) of 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(3-bromophenyl)acetamide hydrochloride in 2 ml of DMF. The reaction mixture is stirred at 80° C. for 18 h. The same amounts of 2-(hydroxymethyl)phenylboronic acid, 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride and sodium hydroxide solution are again added, and the mixture is heated at 80° C. for a further 24 h. The reaction mixture is cooled, filtered through kieselguhr and then purified by preparative HPLC. The product fractions are concentrated, taken up in methanol, mixed with 4M HCl in dioxane and again concentrated. Drying under high vacuum results in 86.5 mg (64.1% of theory) of the title compound.

Workup

  1. temperaturethe mixture is heated at 80° C. for a further 24 h
  2. temperatureThe reaction mixture is cooled
  3. filtrationfiltered through kieselguhr
  4. custompurified by preparative HPLC
  5. concentrationThe product fractions are concentrated
  6. additionmixed with 4M HCl in dioxane
  7. concentrationagain concentrated
  8. customDrying under high vacuum

Sources & evidence

ORD record
ord-7e00672742e84dc58fb7156b21c05063
Source dataset
uspto-grants-2006_11
Patent number
US07138410B2

Reaction notes

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