Acetic Anhydride → 6-Cyano-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

HRID 1380096Notes

Reaction equation

HRID 1380096 reaction equation
[CH:1]([C:3]1[NH:8][C:7]([CH3:9])=[C:6]([C:10]([OH:12])=[O:11])[CH:5]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[CH:14]=2)[C:4]=1[C:22]([O:24][CH3:25])=[O:23])=O.S(O)(O)(=O)=O.[NH2:31]O.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>C(O)(=O)C.C(OCC)(=O)C>[C:1]([C:3]1[NH:8][C:7]([CH3:9])=[C:6]([C:10]([OH:12])=[O:11])[CH:5]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[CH:14]=2)[C:4]=1[C:22]([O:24][CH3:25])=[O:23])#[N:31]

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 159255Hydroxylamine, sulfate (1:1)HCID 517045Sodium AcetateHCID 202420636-Formyl-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

Product 1

HCID 153887666-Cyano-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acidYield 77.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-nitrooxy-2,2-bis(nitrooxymethyl)propyl ester of 6-formyl-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (3.00 g) in acetic acid (15 ml) were added hydroxylamine sulfate (2:1) (0.49 g) and sodium acetate (0.57 g), followed by stirring at ambient temperature for an hour. To the resulting mixture was added acetic anhydride (15 ml), followed by stirring at ambient temperature for 2 hours and under reflux for additional 2 hours. The reaction mixture was evaporated under reduced pressure and the residue obtained was dissolved in ethyl acetate. This solution was successively washed with water, an aqueous sodium bicarbonate and an aqueous sodium chloride, followed by drying over anhydrous magnesium sulfate. After removal of the solvent, the residual oily product (3.6 g) was subjected to column chromatography using silica gel (90 g). Elution was carried out with a mixture of ethyl acetate and toluene (1:10 to 1:4 by volume) and the fractions containing the desired compound were collected and evaporated to give 3-nitrooxy-2,2-bis(nitrooxymethyl)propyl ester of 6-cyano-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1.0 g).

Workup

  1. stirringby stirring at ambient temperature for 2 hours
  2. temperatureunder reflux for additional 2 hours
  3. customThe reaction mixture was evaporated under reduced pressure
  4. customthe residue obtained
  5. washThis solution was successively washed with water
  6. dry with materialby drying over anhydrous magnesium sulfate
  7. customAfter removal of the solvent
  8. washElution
  9. additionwas carried out with a mixture of ethyl acetate and toluene (1:10 to 1:4 by volume)
  10. additionthe fractions containing the desired compound
  11. customwere collected
  12. customevaporated

Sources & evidence

ORD record
ord-e8fc9439477a42c48577fcf701f819a3
Source dataset
uspto-grants-1986_04
Patent number
US04579859

Reaction notes

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