Pyrrolidine → Methyl 4-[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]pyrimidine-2-carboxylate

HRID 873547Notes

Reaction equation

HRID 873547 reaction equation
[CH3:1][C:2]1([CH3:10])[CH2:9][C:7](=[O:8])[CH2:6][C:4](=[O:5])[CH2:3]1.N1CCC[CH2:12]1.[CH:16]([C:18]1[C:19]([CH3:36])=[C:20]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([C:32]([O:34][CH3:35])=[O:33])[N:27]=2)[CH:21]=[CH:22][C:23]=1[O:24][CH3:25])=O.O.[C:38]1([CH3:48])[CH:43]=[CH:42][C:41](S(O)(=O)=O)=C[CH:39]=1.[C:49](=[O:52])([O-])O.[Na+]>C(O)C.C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH3:25][O:24][C:23]1[CH:22]=[CH:21][C:20]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([C:32]([O:34][CH3:35])=[O:33])[N:27]=2)=[C:19]([CH3:36])[C:18]=1[CH:16]1[C:41]2[C:49](=[O:52])[CH2:12][C:38]([CH3:39])([CH3:48])[CH2:43][C:42]=2[O:5][C:4]2[CH2:3][C:2]([CH3:10])([CH3:1])[CH2:9][C:7](=[O:8])[C:6]1=2

Participants

9

Reactant 5

HCID 31268PyrrolidineHCID 31358DimedoneHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 117700769Methyl 4-(3-formyl-4-methoxy-2-methylphenyl)pyrimidine-2-carboxylate

Product 1

HCID 117700535Methyl 4-[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]pyrimidine-2-carboxylateYield 95%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Dimedone (127 mg, 0.907 mol) and pyrrolidine (34.4 μL, 0.0412 mmol) were added to a suspension of the methyl 4-(3-formyl-4-methoxy-2-methylphenyl)pyrimidine-2-carboxylate obtained in Example 75-2 (118 mg, 0.412 mmol) in ethanol (2.0 mL) at room temperature, and the mixture thus obtained was then stirred at 80° C. for 1.5 hours. Thereafter, the reaction solution was cooled to room temperature, and the solvent was then distilled away under reduced pressure. The residue thus obtained was dissolved in chloroform (2.0 mL), and p-toluenesulfonic acid monohydrate (23.5 mg, 0.124 mmol) was then added to the solution thus obtained at room temperature. The mixture thus obtained was stirred at 70° C. for 1 hour. Thereafter, the reaction solution was cooled to room temperature, and a saturated aqueous solution of sodium hydrogen carbonate was then added to the reaction solution. The mixed solution was extracted with dichloromethane twice, and the organic layer thus obtained was then dried over anhydrous sodium sulfate. After that, the solvent was distilled away under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to 0:1, v/v) to obtain the title compound (209 mg, yield: 95%).

Workup

  1. customthe mixture thus obtained
  2. temperatureThereafter, the reaction solution was cooled to room temperature
  3. distillationthe solvent was then distilled away under reduced pressure
  4. customThe residue thus obtained
  5. customthus obtained at room temperature
  6. customThe mixture thus obtained
  7. stirringwas stirred at 70° C. for 1 hour
  8. temperatureThereafter, the reaction solution was cooled to room temperature
  9. extractionThe mixed solution was extracted with dichloromethane twice
  10. customthe organic layer thus obtained
  11. dry with materialwas then dried over anhydrous sodium sulfate
  12. distillationAfter that, the solvent was distilled away under reduced pressure
  13. customThe residue thus obtained
  14. customwas purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-fe1230d763714f9f9aaa72fa9226d99f
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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