Acetoacetic Acid → HCID 53772019, compound

HRID 1380093Notes

Reaction equation

HRID 1380093 reaction equation
[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:11]([OH:17])(=[O:16])[CH2:12][C:13]([CH3:15])=[O:14].C(O)(=O)C.N1CCCCC1>C1C=CC=CC=1.O>[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[C:12]([C:13]([CH3:15])=[O:14])[C:11]([OH:17])=[O:16]

Participants

7

Reactant 4

HCID 96Acetoacetic AcidHCID 176Acetic AcidHCID 8082PiperidineHCID 357452,3-Dichlorobenzaldehyde

Product 1

HCID 53772019HCID 53772019, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 2,3-dichlorobenzaldehyde (0.88 g), 3-nitrooxy-2,2-bis(nitrooxymethyl)propyl ester of acetoacetic acid (1.78 g), acetic acid (25 mg), and piperidine (17 mg) in benzene (10 ml) was refluxed for 1.5 hours, during which time water formed was removed azeotropically. The resulting mixture was cooled to 25° C., washed successively with water, an aqueous sodium bicarbonate and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 3-nitrooxy-2,2-bis(nitrooxymethyl)propyl ester of 2-(2,3-dichlorobenzylidene)acetoacetic acid. To this product, which was dissolved in tert-butyl alcohol (3 ml), was added 2-(N-benzyl-N-methylamino)ethyl 3-aminocrotonate (1.24 g). The resulting mixture was stirred for 5 hours at 80° C., cooled to 25° C., and then concentrated under reduced pressure. The obtained residue in chloroform (50 ml) was washed twice with 2N hydrochloric acid (10 ml each) and water. The chloroform layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give yellow viscous oil. The oil was subjected to column chromatography on silica gel (90 g) and eluted with a mixture of chloroform and methanol (30:1 by volume). The fractions containing the desired company were concentrated under reduced pressure. The obtained residue in ethanol was treated with hydrogen chloride in ethanol. The solvent was removed by distillation under reduced pressure to give amorphous yellow powders of 3-nitrooxy-2,2-bis(nitrooxymethyl)propyl ester of 5-[2-(N-benzyl-N-methylamino)ethoxycarbonyl]-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylic acid hydrochloride (1.95 g).

Workup

  1. customformed
  2. customwas removed azeotropically
  3. washwashed successively with water
  4. dry with materialan aqueous sodium bicarbonate and water, dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a8bcc0f3c0c54d969e125928af114abe
Source dataset
uspto-grants-1986_04
Patent number
US04579859

Reaction notes

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