Formaldehyde → Ethyl 4-Methoxyatropate

HRID 1859335Notes

Reaction equation

HRID 1859335 reaction equation
[CH2:1](OC(=O)C(OCC)=O)C.[H-].[Na+].[CH2:13]([O:15][C:16](=[O:26])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[CH3:14].C=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C1C=CC=CC=1.O>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([C:17](=[CH2:1])[C:16]([O:15][CH2:13][CH3:14])=[O:26])=[CH:19][CH:20]=1

Participants

9

Reactant 5

HCID 712FormaldehydeHCID 7268Diethyl OxalateHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 84174Ethyl 4-methoxyphenylacetate

Product 1

HCID 11275761Ethyl 4-MethoxyatropateYield 94%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of oxalic acid diethyl ester (18.8 ml, 0.14 mol) in tetrahydrofuran (10 ml) and benzene (10 ml) was added sodium hydride (80% oil suspension, 6.5 g, 0.22 mol) and then stirred for 10 minutes under argon atmosphere. A benzene solution (100 ml) of 2-(p-methoxyphenyl)acetic acid ethyl ester (1) (27.0 g, 0.14 mol) was added to the resulting solution and stirred for 3 days at room temperature. The reaction solution was quenched with aqueous 2N HCl solution and extracted with ether. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and then distilled under reduced pressure to remove the solvent. Thus, 48.0 g of the crude product was obtained. The obtained crude product was dissolved in water (150 ml) and 37% formalin (25 ml, 0.31 mol) was added dropwise thereto. To the reaction mixture was added dropwise aqueous potassium carbonate solution (24 g, 0.17 mol, 100 ml) and then stirred for 24 hours. The reaction solution was extracted with ether, and the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained crude product was then purified with silica gel column chromatography (ethyl acetate:hexane=1:5) to obtain 27.0 g (yield: 94%) of ethyl α-(4-methoxyphenyl)acrylate (2).

Workup

  1. stirringstirred for 3 days at room temperature
  2. customThe reaction solution was quenched with aqueous 2N HCl solution
  3. extractionextracted with ether
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThus, 48.0 g of the crude product was obtained
  9. customThe obtained crude product
  10. stirringstirred for 24 hours
  11. extractionThe reaction solution was extracted with ether
  12. washthe organic layer was washed with saturated saline
  13. dry with materialdried over anhydrous magnesium sulfate
  14. distillationdistilled under reduced pressure
  15. customto remove the solvent
  16. customThe obtained crude product
  17. customwas then purified with silica gel column chromatography (ethyl acetate:hexane=1:5)

Sources & evidence

ORD record
ord-07d2826843114f4f9d3b0337180a1972
Source dataset
uspto-grants-2000_11
Patent number
US06153768

Reaction notes

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