Dichloromethane → 2-Chloro-4-[5-chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile

HRID 1897598Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1897598
[Cl:1][C:2]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[C:20]1[CH:21]=[N:22][CH:23]=[C:24]([Cl:29])[C:25]=1[CH:26]([OH:28])[CH3:27].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>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]>[Cl:1][C:2]1[CH:9]=[C:8]([C:20]2[CH:21]=[N:22][CH:23]=[C:24]([Cl:29])[C:25]=2[CH:26]([OH:28])[CH3:27])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 579261132-Chloro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 671550211-(3-Bromo-5-chloro-pyridin-4-yl)-ethanol

Produkt 1

HCID 711049252-Chloro-4-[5-chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrileAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To the solution of 2-Chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (412 mg, 1.56 mmol), 1-(3-Bromo-5-chloro-pyridin-4-yl)-ethanol (370 mg, 1.56 mmol) and PdCl2(dppf). CH2Cl2 adduct (64 mg, 0.08 mmol) in DMF (10 mL) was added 2M Na2CO3 solution (2.35 ml, 4.70 mmol) under Nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 4 hrs. After letting cool to room temperature, solvent was removed in vacuo. The resulting residue was dissolved in DCM and saturated NH4Cl solution. After extraction with DCM and separation, the combined extracts were concentrated and purified by ISCO 12 g (0-30%, EtOAc/Heptane, v/v) to give 2-Chloro-4-[5-chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile (150 mg, 33%) as colorless solid; ESI-MS m/z: 293 [M+H]+,

Aufarbeitung

  1. temperatureAfter letting cool to room temperature
  2. customsolvent was removed in vacuo
  3. dissolutionThe resulting residue was dissolved in DCM
  4. extractionAfter extraction
  5. customwith DCM and separation
  6. concentrationthe combined extracts were concentrated
  7. custompurified by ISCO 12 g (0-30%, EtOAc/Heptane, v/v)

Quellen und Nachweise

ORD-Eintrag
ord-206d2d1822484f35ad64ad584e98475d
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08519134B2

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