Acetic Anhydride → 4-Ethoxy-3-(4-pyridyl)-3-buten-2-one

HRID 1649477Notes

Reaction equation

HRID 1649477 reaction equation
[CH3:1][C:2]([CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1)=[O:3].[CH:11](OCC)(OCC)[O:12][CH2:13][CH3:14].C(OC(=O)C)(=O)C>C(O)(=O)C>[CH3:1][C:2]([C:4]([C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1)=[CH:11][O:12][CH2:13][CH3:14])=[O:3]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 805524-Pyridinylacetone

Product 1

HCID 30212274-Ethoxy-3-(4-pyridyl)-3-buten-2-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In one of its aspects, the invention resides in the three-step process which comprises reacting pyridinylmethyl lower-alkyl ketone of the formula ##STR1## with tri-(lower-alkyl)orthoformate, acetic anhydride and acetic acid to produce 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketone of formula II, ##STR2## reacting said ketone (II) with cyanoacetamide or malonamide in the presence of a basic condensing agent and neutralizing the reaction mixture to produce 1,2-dihydro-6-R-2-oxo-5-PY-nicotinonitrile or 1,2-dihydro-6-R-2-oxo-5-PY-nicotinamide of formula III, ##STR3## where R and R' are each lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, and Q is cyano or carbamyl, respectively. In preferred embodiments 4(or 3)-pyridinylmethyl methyl ketone is first reacted with triethyl or trimethyl orthoformate, acetic anhydride and acetic acid to produce 2-ethoxy(or methoxy)-1-(4- or 3-pyridinyl)ethenyl methyl (or ethyl) ketone, the latter ketone is next reacted with cyanoacetamide or malonamide in the presence of an alkali lower-alkoxide, preferably sodium methoxide, and then the reaction mixture is neutralized to produce 1,2-dihydro-6-methyl(or ethyl)-2-oxo-5-[4(or 3)-pyridinyl]-nicotinonitrile or 1,2-dihydro-6-methyl(or ethyl)-2-oxo-5-[4(or 3)-pyridinyl]nicotinamide, respectively. In a particularly preferred embodiment 4-pyridinylmethyl methyl ketone is first reacted with triethyl orthoformate, acetic anhydride and acetic acid to produce 2-ethoxy-1-(4-pyridinyl)ethenyl methyl ketone, said latter ketone is reacted with cyanoacetamide in the presence of sodium methoxide, and the reaction mixture is neutralized to produce 1,2-dihydro-6-methyl-2-oxo-5-(4-pyridinyl)nicotinonitrile.

Sources & evidence

ORD record
ord-64c7d93a730e4925b6af6cb5dee83b0f
Source dataset
uspto-grants-1983_11
Patent number
US04417054

Reaction notes

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