(4-Methoxyphenyl)boronic acid → 2-Chloro-6-(4-methoxyphenyl)-4-(4-phenoxyphenyl)nicotinonitrile

HRID 81020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 81020
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[C:3]=1[C:4]#[N:5].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:1][C:2]1[N:9]=[C:8]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)[CH:7]=[C:6]([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:15][CH:16]=2)[C:3]=1[C:4]#[N:5]

Komponenten

7

Edukt 3

HCID 201262(4-Methoxyphenyl)boronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 866656822,6-Dichloro-4-(4-phenoxyphenyl)nicotinonitrile

Produkt 1

HCID 866656812-Chloro-6-(4-methoxyphenyl)-4-(4-phenoxyphenyl)nicotinonitrileAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile (110 mg, 0.322 mmol), 4-methoxyphenylboronic acid (53.9 mg, 0.355 mmol), palladium tetrakis(triphenylphosphine) (16.30 mg, 0.016 mmol) and potassium phosphate tribasic monohydrate (0.484 mL, 0.967 mmol) in N,N-dimethylformamide (3 mL) was heated under nitrogen to 100° C. for 15 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (80 mL), washed with water (15 mL), brine (15 mL), dried (MgSO4), and concentrated. Silica gel chromatography, loading with toluene and eluting with 5-30% ethyl acetate in hexanes, gave 2-chloro-6-(4-methoxyphenyl)-4-(4-phenoxyphenyl)nicotinonitrile as white solid (90 mg, 68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.94-8.22 (2H, m), 7.69 (1H, s), 7.56-7.65 (2H, m), 7.42 (2H, t, J=7.97 Hz), 7.18-7.26 (1H, m), 7.06-7.19 (4H, m), 7.02 (2H, δ, J=8.80 Hz), 3.90 (3H, s); MS (ES+) m/z: 413 (M+H); LC retention time: 4.423 min (analytical HPLC Method A).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (15 mL), brine (15 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. washeluting with 5-30% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-4bea9dab0c4d44ed903018e078dbd743
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846673B2

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