2,2-Dimethyl-1,3-dioxane-4,6-dione → Ethyl 4-{[4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridin-2-yl]methoxy}acetoacetate

HRID 1589149Notes

Reaction equation

HRID 1589149 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH3:18])[NH:11][C:10]([CH2:19][O:20][CH2:21][C:22]([OH:24])=O)=[C:9]1[C:25]([O:27][CH2:28][CH3:29])=[O:26].C(N1C=CN=C1)(N1C=CN=C1)=O.[Na].[CH3:43][C:44]1(C)[O:49]C(=O)[CH2:47][C:46](=O)[O:45]1.[H-].[Na+]>O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH3:18])[NH:11][C:10]([CH2:19][O:20][CH2:21][C:22](=[O:24])[CH2:43][C:44]([O:45][CH2:46][CH3:47])=[O:49])=[C:9]1[C:25]([O:27][CH2:28][CH3:29])=[O:26]

Participants

8

Reactant 5

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dione2×HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 5360545SodiumHCID 13457220{[4-(2-Chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}acetic acid

Product 1

HCID 70044209Ethyl 4-{[4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridin-2-yl]methoxy}acetoacetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-{[4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridin-2-yl]methoxy}acetic acid (4.24 g) in tetrahydrofuran (60 ml) was treated with ice-cooling with carbonyldiimidazole (1.70 g) and the mixture stirred at 0° C. for 2.25 hours. This solution was added dropwise over 10 minutes to a solution of the sodium salt of 2,2-dimethyl-1,3-dioxane-4,6-dione in dimethylformamide (prepared by stirring a mixture of 2,2-dimethyl-1,3-dioxane-4,6-dione (1.44 g) and sodium hydride (0.30 g; 80% dispersion in oil) in dimethylformamide (30 ml) with ice-cooling for 30 minutes) and the mixture stirred for 16 hours at room temperature and then evaporated. The residue was dissolved in dichloromethane, washed twice with 1M hydrochloric acid and water, dried (MgSO4), and evaporated. A solution of the residual oil (6 g) in ethanol (50 ml) was heated under reflux for 6 hours and evaporated. The residue was dissolved in diethyl ether, washed twice with 10% aqueous sodium carbonate and once with saturated aqueous sodium chloride, dried (MgSO4), and evaporated. The residue was purified by chromatography on silica (30 g) using hexane plus 5-15% v/v ethyl acetate as eluant. Appropriate fractions were combined and evaporated and the residue crystallised from ethanol to give the title compound (1.5 g), m.p. 88°-89° C. Found: C,58.18; H,5.73; N,2.85. C24H28ClNO8 requires: C,58.36; H,5.71; N,2.84%.

Workup

  1. customprepared
  2. stirringby stirring
  3. temperaturecooling for 30 minutes) and the mixture
  4. stirringstirred for 16 hours at room temperature
  5. customevaporated
  6. dissolutionThe residue was dissolved in dichloromethane
  7. washwashed twice with 1M hydrochloric acid and water
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. temperatureA solution of the residual oil (6 g) in ethanol (50 ml) was heated
  11. temperatureunder reflux for 6 hours
  12. customevaporated
  13. dissolutionThe residue was dissolved in diethyl ether
  14. washwashed twice with 10% aqueous sodium carbonate and once with saturated aqueous sodium chloride
  15. dry with materialdried (MgSO4)
  16. customevaporated
  17. customThe residue was purified by chromatography on silica (30 g)
  18. customevaporated
  19. customthe residue crystallised from ethanol

Sources & evidence

ORD record
ord-05d0459c391c48d890731c91d3bec0f0
Source dataset
uspto-grants-1986_02
Patent number
US04568677

Reaction notes

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