Dimethylformamide → (R,Z)-4-(3-(hydroxyimino)-3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1-o-tolylpropyl)benzonitrile

HRID 1618050Notes

Reaction equation

HRID 1618050 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[CH2:9]/[C:10](/[C:13]2[CH:14]=[CH:15][C:16](=[O:20])[N:17]([CH3:19])[CH:18]=2)=[N:11]\[OH:12])=[CH:4][CH:3]=1.[CH3:28][N:29](C)C=O>O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N.[Zn].C([O-])(=O)C.[Zn+2].C([O-])(=O)C>[OH:12]/[N:11]=[C:10](/[C:13]1[CH:14]=[CH:15][C:16](=[O:20])[N:17]([CH3:19])[CH:18]=1)\[CH2:9][C@H:8]([C:5]1[CH:4]=[CH:3][C:2]([C:28]#[N:29])=[CH:7][CH:6]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:27].[OH:12]/[N:11]=[C:10](\[C:13]1[CH:14]=[CH:15][C:16](=[O:20])[N:17]([CH3:19])[CH:18]=1)/[CH2:9][C@H:8]([C:5]1[CH:4]=[CH:3][C:2]([C:28]#[N:29])=[CH:7][CH:6]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:27]

Participants

10

Reactant 2

HCID 6228DimethylformamideHCID 580434425-[(E)-C-[(2R)-2-(4-bromophenyl)-2-(2-methylphenyl)ethyl]-N-hydroxycarbonimidoyl]-1-methylpyridin-2-one

Product 2

HCID 58043359(R,Z)-4-(3-(hydroxyimino)-3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1-o-tolylpropyl)benzonitrileYield 9%HCID 58043588(R,E)-4-(3-(hydroxyimino)-3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1-o-tolylpropyl)benzonitrileYield 6%

Reagents, catalysts & solvents 6

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11192Zinc AcetateCatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

To a microwave vial was added (R)-5-(3-(4-bromophenyl)-1-(hydroxyimino)-3-o-tolylpropyl)-1-methylpyridin-2(1H)-one (example 223; 98 mg, 230 μmol), 1,1′-bis(diphenyl-phosphino)ferrocene (3.83 mg, 6.91 μmol), tris(dibenzylideneacetone)dipalladium(0) (2.11 mg, 2.3 μmol), zinc cyanide (14.9 mg, 127 μmol), zinc (0.6 mg, 9 μmol) and zinc acetate (1.69 mg, 9.22 μmol) in N,N-dimethylformamide (1.5 mL) and water (15 μl). The vial was capped and heated at 180° C. for 35 min, then at 200° C. for 10 min, then the reaction mixture was concentrated in vacuo and the residue purified by chromatography (SiO2, gradient dichloro-methane to dichloromethane/methanol/25% aq. ammonia solution 95:5:0.25) to produce (R,E)-4-(3-(hydroxyimino)-3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1-o-tolylpropyl)benzonitrile (8 mg, 9%; dark brown gum, MS (ESI+): m/z=: 372.2 [M+H]+) and (R,Z)-4-(3-(hydroxyimino)-3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1-o-tolylpropyl)benzonitrile (6 mg, 6%; dark brown gum, MS (ESI+): m/z=: 372.2 [M+H]+).

Workup

  1. customThe vial was capped
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by chromatography (SiO2, gradient dichloro-methane to dichloromethane/methanol/25% aq. ammonia solution 95:5:0.25)

Sources & evidence

ORD record
ord-6a83ae22d7e04f54adc1d2ac9465b21f
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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