Ethanol → 2,6-Dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-[2-(4-hydroxyphenyl)ethoxycarbonyl]-1,4-dihydropyridine

HRID 1982248Notes

Reaction equation

HRID 1982248 reaction equation
C(O[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH2:16][O:17][C:18](=[O:23])[CH2:19][C:20]([CH3:22])=O)C1C=CC=CC=1.[NH2:24]/[C:25](/[CH3:31])=[CH:26]\[C:27]([O:29][CH3:30])=[O:28].[N+:32]([C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[CH:38]=O)([O-:34])=[O:33].C([OH:45])C>>[CH3:31][C:25]1[NH:24][C:20]([CH3:22])=[C:19]([C:18]([O:17][CH2:16][CH2:15][C:10]2[CH:11]=[CH:12][C:13]([OH:45])=[CH:14][CH:9]=2)=[O:23])[CH:38]([C:37]2[CH:40]=[CH:41][CH:42]=[C:35]([N+:32]([O-:34])=[O:33])[CH:36]=2)[C:26]=1[C:27]([O:29][CH3:30])=[O:28]

Participants

5

Reactant 4

HCID 702EthanolHCID 74493-NitrobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 1317147162-(Benzyloxyphenyl)ethylacetoacetate

Product 1

HCID 201974812,6-Dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-[2-(4-hydroxyphenyl)ethoxycarbonyl]-1,4-dihydropyridine

Procedure

Similarly, 30 g of 2-[4-(t-butoxycarbonylamino)phenyl)ethylacetate (9), 11.5 g of methyl β-aminocrotonate, and 15.1 g of 3-nitrobenzaldehyde in 200 ml of ethanol was heated at reflux for 12 h. The solvent was removed under reduced pressure and the residue of crude 1,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-[2-(4-t-butoxycarbonylaminophenyl)ethoxycarbonyl]-1,4-dihydropyridine dissolved in 100 ml of dichloromethane and 100 ml of formic acid. The mixture was heated on a steam bath for 20 min., followed by solvent removal under reduced pressure. The residue was partitioned between 5% aqueous HCl and ethyl acetate, and the aqueous layer basified with NaOH and extracted with ether. The ether was dried and evaporated, and the residue crystallized from ethyl acetate-hexane to afford 20.4 g of 2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-[2-(4-aminophenyl)ethoxycarbonyl]-1,4-dihydropyridine (11), m.p. 107°-109° C. Calculated for C24H25N3O 6 : C-63.84, H-5.59, N-9.31. Found: C-63.99, H-5.69, N-9.13.

Workup

  1. temperatureat reflux for 12 h
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue of crude 1,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-[2-(4-t-butoxycarbonylaminophenyl)ethoxycarbonyl]-1,4-dihydropyridine dissolved in 100 ml of dichloromethane
  4. temperatureThe mixture was heated on a steam bath for 20 min.
  5. customfollowed by solvent removal under reduced pressure
  6. customThe residue was partitioned between 5% aqueous HCl and ethyl acetate
  7. extractionextracted with ether
  8. dry with materialThe ether was dried
  9. customevaporated
  10. customthe residue crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-a4bad8a498d44e429cd2134052d40c2b
Source dataset
uspto-grants-1986_06
Patent number
US04595690

Reaction notes

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