Acetic Anhydride → 2-Ethoxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-cyano-1,4-dihydropyridine-3-carboxylate

HRID 894680Notes

Reaction equation

HRID 894680 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH:30]=O)=[C:5]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:6]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12][O:13][CH2:14][CH3:15])=[O:9].Cl.[NH2:33]O.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>C(O)(=O)C>[CH3:1][C:2]1[NH:3][C:4]([C:30]#[N:33])=[C:5]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:6]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12][O:13][CH2:14][CH3:15])=[O:9]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 133883552-Ethoxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-formyl-1,4-dihydropyridine-3-carboxylate

Product 1

HCID 133883342-Ethoxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-cyano-1,4-dihydropyridine-3-carboxylateYield 50.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 2-ethoxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-formyl-1,4-dihydropyridine-3-carboxylate (3.00 g), hydroxylamine hydrochloride (0.5547 g), sodium acetate (1.1382 g) in acetic acid (10 ml) was stirred for 30 minutes at room temperature. To this mixture was added acetic anhydride (1.4 ml) and the resultant mixture was stirred for an hour at room temperature and refluxed for an hour. The acetic acid was distilled off under reduced pressure, and to the residue was added water. The resultant mixture was neutrallized with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate twice. The extract was washed with water and an aqueous solution saturated with sodium chloride and dried. The solvent was distilled off and thus obtained viscous oily substance (3.19 g) was subjected to column chromatography on silica gel with an eluent [a mixture of 5 parts of benzene and one part of ethyl acetate by volume] and a yellow oil (1.74 g) was obtained from the fraction which contained the designated product. The oil turned into crystals (1.56 g). These crystals were recrystallized from benzene to give yellow powder (1.5 g) of 2-ethoxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-cyano-1,4-dihydropyridine-3-carboxylate.1/3benzene, m.p. 89° to 91° C. Thus obtained yellow powder was further recrystallized from a mixture of diethyl ether and n-hexane to give crystals of 2-ethoxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-cyano-1,4-dihydropyridine-3-carboxylate, m.p. 115° to 116° C.

Workup

  1. temperaturerefluxed for an hour
  2. distillationThe acetic acid was distilled off under reduced pressure
  3. additionto the residue was added water
  4. extractionextracted with ethyl acetate twice
  5. washThe extract was washed with water
  6. dry with materialan aqueous solution saturated with sodium chloride and dried
  7. distillationThe solvent was distilled off
  8. additiona mixture of 5 parts of benzene and one part of ethyl acetate by volume] and a yellow oil (1.74 g)
  9. customwas obtained from the fraction which
  10. customThese crystals were recrystallized from benzene

Sources & evidence

ORD record
ord-8de2cdc657e94be39a2d5006b5434ebf
Source dataset
uspto-grants-1981_08
Patent number
US04284634

Reaction notes

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