2-Chlorobenzaldehyde → {[4-(2-Chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}acetic acid

HRID 462458Notes

Reaction equation

HRID 462458 reaction equation
C[O:2][C:3]([CH2:5][O:6][CH2:7][C:8](=O)[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:4].[Cl:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]=O.[NH2:25]/[C:26](/[CH3:32])=[CH:27]\[C:28]([O:30][CH3:31])=[O:29]>CO>[Cl:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]1[C:27]([C:28]([O:30][CH3:31])=[O:29])=[C:26]([CH3:32])[NH:25][C:8]([CH2:7][O:6][CH2:5][C:3]([OH:2])=[O:4])=[C:9]1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

5

Reactant 3

HCID 69962-ChlorobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 13457217Ethyl 4-(methoxycarbonylmethoxy)acetoacetate

Product 1

HCID 13457220{[4-(2-Chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}acetic acidYield 16.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ethyl 4-(methoxycarbonylmethoxy)acetoacetate (200 g), 2-chlorobenzaldehyde (128.8 g) and methyl 3-aminocrotonate (105.4 g) in methanol (600 ml) was heated under reflux for 16 hours and then evaporated. The residue was treated with 10% aqueous sodium hydroxide solution and the mixture heated under reflux for 1.5 hours, allowed to cool to room temperature, washed three times with dichloromethane, acidified with concentrated hydrochloric acid and extracted into dichloromethane. The dichloromethane extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was recrystallised from ethyl acetate to give the title compound (63 g), m.p. 150°-154° C.

Workup

  1. temperatureunder reflux for 16 hours
  2. customevaporated
  3. additionThe residue was treated with 10% aqueous sodium hydroxide solution
  4. temperaturethe mixture heated
  5. temperatureunder reflux for 1.5 hours
  6. washwashed three times with dichloromethane
  7. extractionextracted into dichloromethane
  8. washThe dichloromethane extracts were washed with water
  9. dry with materialdried over magnesium sulphate
  10. customevaporated
  11. customThe residue was recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-e1449e369550492ab65cb2a15f2fb1c0
Source dataset
uspto-grants-1985_05
Patent number
US04515799

Reaction notes

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