Methyl acetoacetate → Dimethyl 2,6-dimethyl-4-[2-(3-thienyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate

HRID 745531Notes

Reaction equation

HRID 745531 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=2[CH:8]=O)=[CH:2]1.[C:14]([O:20][CH3:21])(=[O:19])[CH2:15][C:16]([CH3:18])=O.[NH2:22]/[C:23](/[CH3:29])=[CH:24]\[C:25]([O:27][CH3:28])=[O:26]>CO.[OH-].[NH4+]>[CH3:18][C:16]1[NH:22][C:23]([CH3:29])=[C:24]([C:25]([O:27][CH3:28])=[O:26])[CH:8]([C:7]2[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=2[C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[C:15]=1[C:14]([O:20][CH3:21])=[O:19]

Participants

6

Reactant 3

HCID 7757Methyl acetoacetateHCID 643918Methyl 3-aminocrotonateHCID 43213152-(3-thienyl)benzaldehyde

Product 1

HCID 13552994Dimethyl 2,6-dimethyl-4-[2-(3-thienyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate

Reagents, catalysts & solvents 2

HCID 14923Ammonium HydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of crude Compound 2c (10.6 mmol) in methanol (10 mL) was added methyl acetoacetate (10.6 mmol), methyl 3-aminocrotonate (10.6 mmol) and concentrated ammonium hydroxide (1 drop). The reaction mixture was heated at reflux under nitrogen for 4 days. The solvent was removed in vacuo and the residue purified by flash chromatography on silica gel eluted with diethyl ether:hexane (2:1) and trituration with diethyl ether:hexane (1:2) to yield Compound 2d as a pale yellow solid (m.p. 164°-166° C.).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux under nitrogen for 4 days
  3. customThe solvent was removed in vacuo
  4. customthe residue purified by flash chromatography on silica gel
  5. washeluted with diethyl ether:hexane (2:1) and trituration with diethyl ether:hexane (1:2)

Sources & evidence

ORD record
ord-5f9594b55376404aafb1603d1e814b05
Source dataset
uspto-grants-1986_07
Patent number
US04599341

Reaction notes

Loading…