Acetoacetic Acid → 5-[2-(N-benzyl-N-methylamino)ethoxycarbonyl]-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylic acid hydrochloride

HRID 1380092Notes

Reaction equation

HRID 1380092 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.[NH2:18]/[C:19](/[CH3:35])=[CH:20]\[C:21]([O:23][CH2:24][CH2:25][N:26]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH3:27])=[O:22]>C(O)(C)(C)C>[ClH:1].[CH2:28]([N:26]([CH2:25][CH2:24][O:23][C:21]([C:20]1[CH:4]([C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([Cl:10])[C:2]=2[Cl:1])[C:12]([C:11]([OH:17])=[O:16])=[C:13]([CH3:15])[NH:18][C:19]=1[CH3:35])=[O:22])[CH3:27])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 96Acetoacetic AcidHCID 357452,3-DichlorobenzaldehydeHCID 125291882-(N-Benzyl-N-methylamino)ethyl 3-amino-2-butenoate

Product 1

HCID 704551485-[2-(N-benzyl-N-methylamino)ethoxycarbonyl]-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylic acid hydrochlorideYield 38%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2,3-dichlorobenzaldehyde (0.70 g), 3-nitrooxy-2,2-bis(nitrooxymethyl)propyl ester of acetoacetic acid (1.42 g) and 2-(N-benzyl-N-methylamino)ethyl 3-aminocrotonate (0.99 g) in tert-butyl alcohol (3 ml) was heated for 2 hours at 60° C. and then refluxed for additional 5.5 hours. The resulting mixture was cooled to 25° C. and concentrated under reduced pressure. The residue obtained was subjected to column chromatography on silica gel (54 g) and eluted with a mixture of chloroform and methanol (100:1 by volume). The fractions containing the desired compound were collected and evaporated under reduced pressure to give yellow viscous oil. The oil was again subjected to column chromatography on silica gel (27 g) and eluted with a mixture of toluene and ethyl acetate (5:2 by volume). The fractions containing the desired compound were collected and evaporated 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 (0.40 g).

Workup

  1. temperaturerefluxed for additional 5.5 hours
  2. concentrationconcentrated under reduced pressure
  3. customThe residue obtained
  4. washeluted with a mixture of chloroform and methanol (100:1 by volume)
  5. additionThe fractions containing the desired compound
  6. customwere collected
  7. customevaporated under reduced pressure
  8. customto give yellow viscous oil
  9. washeluted with a mixture of toluene and ethyl acetate (5:2 by volume)
  10. additionThe fractions containing the desired compound
  11. customwere collected
  12. customevaporated under reduced pressure
  13. additionThe obtained residue in ethanol was treated with hydrogen chloride in ethanol
  14. customThe solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-abaa1350a0b6461b8e4c78a0d13fc31c
Source dataset
uspto-grants-1986_04
Patent number
US04579859

Reaction notes

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