Dichloromethane → 4-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile

HRID 1499696Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1499696
Br[C:2]1[C:3]([O:13][CH3:14])=[C:4]([CH:10]([OH:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([C:29]#[N:30])[CH:24]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C(#N)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].O>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([C:29]#[N:30])[CH:24]=2)[C:3]([O:13][CH3:14])=[C:4]([CH:10]([OH:12])[CH3:11])[CH:5]=1

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 457862934-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrileHCID 866668161-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol

Produkt 1

HCID 866776404-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A mixture of 1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol (0.30 g, 1.1 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrile (from Combi-Blocks, 0.27 g, 1.2 mmol), sodium carbonate (230 mg, 2.1 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (100 mg, 0.13 mmol) in acetonitrile (8 mL)/water (2 mL) was degassed and then refilled with N2. The reaction was stirred at 95° C. for 2 hours, then cooled and diluted with ethyl acetate, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with 0 to 40% EtOAc in hexanes (0.249 g, 75%). LCMS calculated for C16H16ClN2O2 (M+H)+: m/z=303.1; Found: 303.0

Aufarbeitung

  1. customwas degassed
  2. additionrefilled with N2
  3. temperaturecooled
  4. additiondiluted with ethyl acetate
  5. washwashed with sat. NaHCO3, water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 0 to 40% EtOAc in hexanes (0.249 g, 75%)

Quellen und Nachweise

ORD-Eintrag
ord-7a1ecbf00e174301b393037fbd97a0f8
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09199982B2

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