Benzenepropanoic acid, 3-bromo-3-oxo-, ethyl ester → 6-(3-Bromophenyl)-4-hydroxy-2-(4-phenoxyphenyl)nicotinonitrile

HRID 81056Notes

Reaction equation

HRID 81056 reaction equation
[NH2:1][C:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)=[CH:3][C:4]#[N:5].[Br:19][C:20]1[CH:21]=[C:22]([C:26](=O)[CH2:27][C:28](OCC)=[O:29])[CH:23]=[CH:24][CH:25]=1>O>[Br:19][C:20]1[CH:21]=[C:22]([C:26]2[NH:1][C:2]([C:6]3[CH:11]=[CH:10][C:9]([O:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[CH:8][CH:7]=3)=[C:3]([C:4]#[N:5])[C:28](=[O:29])[CH:27]=2)[CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 179368Benzenepropanoic acid, 3-bromo-3-oxo-, ethyl esterHCID 669270523-Amino-3-(4-phenoxyphenyl)acrylonitrile

Product 1

HCID 669269356-(3-Bromophenyl)-4-hydroxy-2-(4-phenoxyphenyl)nicotinonitrileYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3-amino-3-(4-phenoxyphenyl)acrylonitrile (0.553 g, 2342 mmol) and ethyl 3-(3-bromophenyl)-3-oxopropanoate (2.540 g, 9.37 mmol) was microwaved at 230° C. for 20 min. After cooling to room temperature, the mixture was diluted with water and extracted with ethyl acetate (100 mL). The ethyl acetate phase was washed with saturated ammonium chloride, brine, dried (MgSO4), and concentrated. Silica gel chromatography, eluting with 0-80% ethyl acetate in hexanes, gave 6-(3-bromophenyl)-4-oxo-2-(4-phenoxyphenyl)-1,4-dihydropyridine-3-carbonitrile as brown solid (0.909 g, 88% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.81 (1H, br. s), 7.70 (2H, δ, J=8.28 Hz), 7.62 (2H, δ, J=7.28 Hz), 7.35 (3H, t, J=7.40 Hz), 7.18 (1H, t, J=7.28 Hz), 7.03 (4H, dd, J=11.92, 8.66 Hz), 6.68 (1H, br. s); MS (ES+) m/z: 443,445 (M+H); LC retention time: 4.361 min (analytical HPLC Method A).

Workup

  1. customwas microwaved at 230° C. for 20 min
  2. extractionextracted with ethyl acetate (100 mL)
  3. washThe ethyl acetate phase was washed with saturated ammonium chloride, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 0-80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e21e7066e92442fd9454086db65fba2c
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

Loading…