Ethyl formate → Ethyl 2-[(2H-1,3-benzodioxol-5-yl)methyl]-3-oxopropanoate

HRID 1445309Notes

Reaction equation

HRID 1445309 reaction equation
[H-].[Na+].[CH2:3]1[O:11][C:10]2[CH:9]=[CH:8][C:7]([CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:6][C:5]=2[O:4]1.[CH:19](OCC)=[O:20].P([O-])([O-])([O-])=O.P([O-])(O)(O)=O.[K+]>C1COCC1.C(#N)C>[CH:19]([CH:13]([CH2:12][C:7]1[CH:8]=[CH:9][C:10]2[O:11][CH2:3][O:4][C:5]=2[CH:6]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:20]

Participants

7

Reactant 4

HCID 8025Ethyl formate4×HCID 24758Sodium hydride4×HCID 81545Ethyl 1,3-benzodioxole-5-propionateHCID 86606725HCID 86606725, compound

Product 1

HCID 10060648Ethyl 2-[(2H-1,3-benzodioxol-5-yl)methyl]-3-oxopropanoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

First 2.0 g of 606 NaH was suspended in 30 ml of THF and the suspension solution was cooled to 0° C. Then, 6.0 g of ethyl 3-(3,4-methylenedioxyphenyl)-propionate (purity: 92.1% by weight) was dissolved in 20 ml of THF and added dropwise to the suspension solution prepared above. After 4 ml of ethyl formate was added at 0° C., the solution was returned to room temperature and stirred for a further 20 minutes. The reaction solution was heated to 40° C. and stirring was further continued. About 30 minutes after heating, gas generation was observed. After completion of gas generation, the reaction solution was analyzed by HPLC (Column: LiChrosphere 100 PR-8(E), 250 mm×4.0 mm I.D., manufactured by Merck Ltd., Mobile phase: an aqueous solution of phosphate/potassium dihydrogenphosphate: acetonitrile=1:1, flow rate: 1 ml/minute, detection wavelength: 210 nm, column temperature: 30° C.), it was observed that raw materials remained. Then, 1 g of NaH and 4 ml of ethyl formate were added to the reaction solution and stirred at 40° C. Gas generation started again and completed in about 15 minutes. As the reaction solution was analyzed again, the raw materials were observed to still remain. Then, 1 g of NaH and 4 ml of ethyl formate were added to the reaction solution. After completion of gas generation, the reaction solution was analyzed again. Since the raw materials were observed to slightly remain, further 1 g of NaH and 8 ml of ethyl formate were added to the reaction solution. Since the raw materials were observed to completely disappear, the reaction was terminated. After pH was adjusted to 7 to 8 with hydrochloric acid, ethyl acetate was added to perform extraction. Mineral oil contained in NaH was removed by a separatory funnel in accordance with a liquid-separatory operation. The obtained ethyl acetate layer was concentrated to obtain 4.75 g of the titled compound as an orange oil. The chemical purity, as analyzed in accordance with the process of Example 1, was 80.20% by weight.

Workup

  1. additionadded dropwise to the suspension solution
  2. customprepared above
  3. customwas returned to room temperature
  4. temperatureThe reaction solution was heated to 40° C.
  5. stirringstirring
  6. temperatureAbout 30 minutes after heating
  7. custom30° C.
  8. stirringstirred at 40° C
  9. waitcompleted in about 15 minutes
  10. customthe reaction was terminated
  11. additionwas added
  12. extractionextraction
  13. customwas removed by a separatory funnel in accordance with a liquid-separatory operation
  14. concentrationThe obtained ethyl acetate layer was concentrated

Sources & evidence

ORD record
ord-7a7b21b5596e4bbb9b37eff1eb21f27f
Source dataset
uspto-grants-2010_02
Patent number
US07666659B2

Reaction notes

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