3-Nitrobenzaldehyde → HCID 12896950, compound

HRID 894710Notes

Reaction equation

HRID 894710 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[CH3:12][O:13][CH:14]([O:22][CH3:23])[C:15](=O)[CH2:16][C:17]([O:19][CH3:20])=[O:18].N1CCCCC1.[NH2:30]/[C:31](/[CH3:37])=[CH:32]\[C:33]([O:35][CH3:36])=[O:34]>C1C=CC=CC=1.C(O)(=O)C>[CH3:37][C:31]1[NH:30][C:15]([CH:14]([O:22][CH3:23])[O:13][CH3:12])=[C:16]([C:17]([O:19][CH3:20])=[O:18])[CH:7]([C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[C:32]=1[C:33]([O:35][CH3:36])=[O:34]

Participants

7

Reactant 4

HCID 74493-NitrobenzaldehydeHCID 8082PiperidineHCID 643918Methyl 3-aminocrotonateHCID 11008445Methyl 4,4-dimethoxy-3-oxobutanoate

Product 1

HCID 12896950HCID 12896950, compoundYield 51.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 241BenzeneSolvent3×

Procedure

To a mixture of 3-nitrobenzaldehyde (7.56 g), methyl 4,4-dimethoxyacetoacetate (9,69 g) and acetic acid (600 mg) in benzene (25 ml) was added portionwise each one fifth portion of piperidine (851 mg) in benzene (5 ml) for each 20 minutes' interval and the mixture was heated to reflux for 4 hours under azeotropic dehydration. After cooling, the reaction mixture was diluted with benzene (50 ml), washed twice with diluted aqueous sodium bicarbonate solution, and in turn, with water and saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated to dryness under reduced pressure to give crude reddish brown oily methyl (3-nitrobenzylidene)-4,4-dimethylacetoacetate (17.82 g) which was used in the following reaction without any further purification. A mixture of above oil (17.82 g) and methyl 3-aminocrotonate (6.33 g) was heated at 60° to 65° C. for 4.5 hours, at 100° to 105° C. for 8 hours and 45 minutes. The reaction mixture was chromatographed on a column of silica-gel (440 g) and eluted with a mixture of benzene and ethyl acetate (10:1, v/v) to give crystalline product (10.46 g) of dimethyl 2-methyl-4-(3-nitrophenyl)-6-dimethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate. Thus obtained crystals (720 mg) were recrystallized from diisopropyl ether (10 ml) to give pure specimen (560 mg), mp 99° to 100° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 hours under azeotropic dehydration
  3. temperatureAfter cooling
  4. washwashed twice with diluted aqueous sodium bicarbonate solution
  5. dry with materialin turn, with water and saturated aqueous solution of sodium chloride, dried over magnesium sulfate
  6. customevaporated to dryness under reduced pressure
  7. customto give crude reddish brown oily methyl (3-nitrobenzylidene)-4,4-dimethylacetoacetate (17.82 g) which
  8. customwas used in the following reaction without any further purification
  9. temperaturewas heated at 60° to 65° C. for 4.5 hours, at 100° to 105° C. for 8 hours and 45 minutes
  10. customThe reaction mixture was chromatographed on a column of silica-gel (440 g)
  11. washeluted with a mixture of benzene and ethyl acetate (10:1

Sources & evidence

ORD record
ord-6ff53d51282646a2950a8835e21545fe
Source dataset
uspto-grants-1981_08
Patent number
US04284634

Reaction notes

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