4-Nitrobenzaldehyde → 2-((4-Nitrophenyl)methylene]-3-oxobutanoic acid 2-cyanoethyl ester

HRID 322168Notes

Reaction equation

HRID 322168 reaction equation
[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:12]([O:18][CH2:19][CH2:20][C:21]#[N:22])(=[O:17])[CH2:13][C:14]([CH3:16])=[O:15]>CC(O)C.N1CCCCC1.C(O)(=O)C>[C:21]([CH2:20][CH2:19][O:18][C:12](=[O:17])[C:13](=[CH:8][C:7]1[CH:10]=[CH:11][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)[C:14](=[O:15])[CH3:16])#[N:22]

Participants

6

Reactant 2

HCID 5414-NitrobenzaldehydeHCID 123604062-Cyanoethyl 3-oxobutanoate

Product 1

HCID 543622242-((4-Nitrophenyl)methylene]-3-oxobutanoic acid 2-cyanoethyl esterYield 64%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 8082PiperidineCatalystHCID 3776IsopropanolSolvent

Procedure

A suspension of 4-nitrobenzaldehyde (5.00 g, 33.0 mmol), 2-cyanoethyl acetoacetate (5.13 g, 33.0 mmol), piperidine (140 mg, 1.65 mmol) and acetic acid (99 mg, 1.7 mmol) in 150 ml of 2-propanol was stirred at r.t. for 48 hrs. Reaction mixture was filtered, the solid collected was dried in air to give 2-[(4-nitrophenyl)methylene]-3-oxobutanoic acid 2-cyanoethyl ester as a white powder (6.08 g, 64%). A solution of 2-[(4-nitrophenyl)methylene)-3-oxobutanoic acid 2-cyanoethyl ester (4.29 g, 14.9 mmol) and 3-amino-N-methylcrotonamide (2.55 g, 22.3 mmol) in 50 ml of EtOH was refluxed for 36 hrs. After solvent was removed, the residue was dissolved in 250 ml of CHCl3 washed with water (2×100 ml) and dried over Na2SO4. After filtration and removal of solvent, 3-(2-cyanoethoxy) carbonyl-1,4-dihydro-2,6-dimethyl-5-(N-methyl) carboxamido-4-(4-nitrophenyl) pyridine was obtain as a yellow powder (7.96 g, 63%). The solution of 3-(2-cyanoethoxy) carbonyl-1,4-dihydro-2,6-dimethyl-5-(N-methyl) carboxamido-4-(4-nitrophenyl) pyridine (2.00 g, 5.20 mmol) in 40 ml acetone was treated with 40 ml 1N KOH solution at 0° C. for 45 min. The acetone was removed in vacuo and aqueous layer was acidified to pH=3 by 2N hydrochloric acid, the yellow precipitation was collected by filtration, washed with 10 ml of cold water and dried in vacuo. 1.53 g (89% yield) of 1,4-dihydro-2,6-dimethyl-5-(N-methyl)carboxamido-4-(4-nitrophenyl)pyridine-3-carboxylic acid was obtained as a yellow powder.

Workup

  1. customReaction mixture
  2. filtrationwas filtered
  3. customthe solid collected
  4. customwas dried in air

Sources & evidence

ORD record
ord-0a5005dc3ea94a4cb9146d74bc038389
Source dataset
uspto-grants-2001_04
Patent number
US06211198B1

Reaction notes

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