Pyrrolidine → Methyl 6-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylate

HRID 873518Notes

Reaction equation

HRID 873518 reaction equation
N1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:6]([C:8]1[C:9]([CH3:26])=[C:10]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][CH:17]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH3:15])=O.[CH3:27][C:28]1([CH3:36])[CH2:33][C:32](=[O:34])[CH2:31][C:30](=[O:35])[CH2:29]1.[OH2:37].[C:38]1([CH3:48])[CH:43]=CC(S(O)(=O)=O)=C[CH:39]=1>C(O)C.C(Cl)(Cl)Cl.CCCCCC.O>[CH3:15][O:14][C:13]1[CH:12]=[CH:11][C:10]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][CH:17]=2)=[C:9]([CH3:26])[C:8]=1[CH:6]1[C:31]2[C:30](=[O:35])[CH2:29][C:28]([CH3:36])([CH3:27])[CH2:33][C:32]=2[O:34][C:2]2[CH2:39][C:38]([CH3:48])([CH3:43])[CH2:5][C:4](=[O:37])[C:3]1=2

Participants

9

Reactant 4

HCID 31268PyrrolidineHCID 31358DimedoneHCID 521998p-Toluenesulfonic acid monohydrateHCID 117700848Methyl 6-(3-formyl-4-methoxy-2-methylphenyl)pyridine-2-carboxylate

Product 1

HCID 117700765Methyl 6-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylateYield 901.2%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 8058HexaneSolvent

Conditions

Temperature
80 °C

Procedure

Pyrrolidine (0.018 ml, 0.22 mmol) was added to a suspension of the methyl 6-(3-formyl-4-methoxy-2-methylphenyl)pyridine-2-carboxylate produced in Example 4-2 (620 mg, 2.17 mmol) and 5,5-dimethylcyclohexane-1,3-dione (701 mg, 5.00 mmol) in ethanol (12.4 ml) at room temperature, and the mixture thus obtained was then stirred at 80° C. for 2 hours. After air-cooling, the solvent was distilled away from the reaction solution under reduced pressure. The residue thus obtained was dissolved in chloroform (12.4 ml), and p-toluenesulfonic acid monohydrate (112 mg, 0.65 mmol) was then added to the solution obtained above. The mixture thus obtained was stirred at 70° C. for 4 hours. After air-cooling, water was added to the reaction solution, and the mixed solution was then extracted with dichloromethane. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then purified by silica gel column chromatography (ethyl acetate:hexane=1:1, v/v) to obtain the title compound (1.05 g, yield: 91%).

Workup

  1. customthe mixture thus obtained
  2. temperatureAfter air-cooling
  3. distillationthe solvent was distilled away from the reaction solution under reduced pressure
  4. customThe residue thus obtained
  5. customobtained above
  6. customThe mixture thus obtained
  7. stirringwas stirred at 70° C. for 4 hours
  8. temperatureAfter air-cooling
  9. extractionthe mixed solution was then extracted with dichloromethane
  10. customThe organic layer thus obtained
  11. dry with materialwas dried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled away under reduced pressure
  13. customthe residue thus obtained
  14. customwas then purified by silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-fb0ade1ecdb24fbfa4b17a7db192be66
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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