Citric Acid → 3-(4-Cyanobenzyl)pyridin-4-carboxylic acid methyl ester

HRID 342624

Reaktionsgleichung

Reaktionsgleichung von HRID 342624
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[CH:5][CH:4]=1)#[N:2].[CH3:11][O:12][C:13]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][C:16]=1Br)=[O:14].CCOC(C)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.[Zn].Cl[Ni](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:11][O:12][C:13]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][C:16]=1[CH2:7][C:6]1[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)=[O:14]

Komponenten

8

Edukt 4

HCID 311Citric AcidHCID 8857Ethyl AcetateHCID 869964-(Bromomethyl)benzonitrileHCID 2762700Methyl 3-bromoisonicotinate

Produkt 1

HCID 539534263-(4-Cyanobenzyl)pyridin-4-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysatorHCID 178418751HCID 178418751, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 4-cyanobenzyl bromide (625 mg, 3.27 mmol) in dry THF (4 mL) was added slowly over ~3 min. to a suspension of activated Zn (dust; 250 mg) in dry THF (2 mL) at 0° under an argon atmosphere. The ice-bath was removed and the slurry was stirred at room temperature for a further 30 min. Then 3-bromopyridin-4-carboxylic acid methyl ester (540 mg. 2.5 mmol) followed by dichlorobis(triphenylphosphine)nickel (II) (50 mg). The resultant reddish-brown mixture was stirred for 3 h at ~40°-45° C. The mixture was cooled and distributed between EtOAc (100 ml,) and 5% aqueous citric acid (50 mL). The organic layer was washed with H2O(2×50 mL), dried with Na2SO4. After evaporation of the solvent the residue was purified on silica gel, eluting with 35% EtOAc in hexane to give 420 mg as a clear gum. FAB ms (M+1)253.

Aufarbeitung

  1. customThe ice-bath was removed
  2. stirringThe resultant reddish-brown mixture was stirred for 3 h at ~40°-45° C
  3. temperatureThe mixture was cooled
  4. washThe organic layer was washed with H2O(2×50 mL)
  5. dry with materialdried with Na2SO4
  6. customAfter evaporation of the solvent the residue
  7. customwas purified on silica gel
  8. washeluting with 35% EtOAc in hexane
  9. customto give 420 mg as a clear gum

Quellen und Nachweise

ORD-Eintrag
ord-b2cf0ecfa5e14d46bc4ce3065a213a40
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859012

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