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

HRID 81020Notes

Reaction equation

HRID 81020 reaction equation
[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]

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4bea9dab0c4d44ed903018e078dbd743
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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