Ammonium Chloride → Methyl 4-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)benzoate

HRID 81060Notes

Reaction equation

HRID 81060 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].C[O:20][C:21](=O)[CH2:22][C:23]([C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=1)=O.[Cl-].[NH4+]>>[C:4]([C:3]1[C:21](=[O:20])[CH:22]=[C:23]([C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=2)[NH:1][C:2]=1[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)#[N:5]

Participants

4

Reactant 3

HCID 25517Ammonium ChlorideHCID 3864207Methyl 4-(3-methoxy-3-oxopropanoyl)benzoateHCID 669270523-Amino-3-(4-phenoxyphenyl)acrylonitrile

Product 1

HCID 66927073Methyl 4-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)benzoateYield 65%

Procedure

A mixture of 3-amino-3-(4-phenoxyphenyl)acrylonitrile (0.517 g, 2.188 mmol) and methyl 4-(3-methoxy-3-oxopropanoyl)benzoate (2.068 g, 8.75 mmol) was microwaved at 230° C. for 20 min. After cooling to room temperature, the mixture was poured into saturated ammonium chloride (25 mL) and extracted with ethyl acetate (80 mL). The ethyl acetate phase was washed with saturated ammonium chloride (10 mL), water (10 mL), brine (5 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0-80% ethyl acetate in hexanes, gave impure products. The material was triturated with dichloromethane. The white solid was collected by filtration to give methyl 4-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)benzoate (0.598 g, 65% yield). 1H NMR (400 MHz, CDCl3) δ ppm 9.25 (1H, br. s), 8.17 (2H, br. s), 8.02 (1H, br. s), 7.71 (2H, br. s), 7.40 (2H, t, J=7.91 Hz), 7.24 (1H, br. s), 7.03-7.16 (4H, m), 6.62 (1H, br. s), 3.95 (3H, s); MS (ES+) m/z: 423 (M−H); LC retention time: 4.118 min (analytical HPLC Method A).

Workup

  1. customwas microwaved at 230° C. for 20 min
  2. extractionextracted with ethyl acetate (80 mL)
  3. washThe ethyl acetate phase was washed with saturated ammonium chloride (10 mL), water (10 mL), brine (5 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 0-80% ethyl acetate in hexanes
  7. customgave impure products
  8. customThe material was triturated with dichloromethane
  9. filtrationThe white solid was collected by filtration

Sources & evidence

ORD record
ord-32dbd12d6901415b9c9597ee06267442
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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