Diethyl (ethoxymethylene)malonate → Diethyl [(3-chloro-4-fluoroanilino)methylidene]propanedioate

HRID 1607994Notes

Reaction equation

HRID 1607994 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].C(O[CH:13]=[C:14]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16])C>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][CH:13]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:6]=[CH:7][C:8]=1[F:9]

Participants

4

Reactant 2

HCID 6871Diethyl (ethoxymethylene)malonateHCID 97083-Chloro-4-fluoroaniline

Product 1

HCID 533801Diethyl [(3-chloro-4-fluoroanilino)methylidene]propanedioateYield 85%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

3-Chloro-4-fluoroaniline (30.08 kg) in 8 L ethanol was heated at 40-50° C until a clear solution was obtained. Said solution was added to a 100 gallon glass-lined unit charged with 196 L ethanol. Diethyl ethoxymethylenemalonate (49.1 kg) was then added over an 80 minute period with stirring. The mixture was brought to reflux for one hour and then cooled to near 0° C. with stirring. Crystallization was initiated with seeding when the temperature had reached 27° C. during the cooling process. Stirring was continued for another hour, the solid product was filtered on a ceramic filter, and the filter cake was washed with 3×16 L cold (1°-5° C.) ethanol. The product was dried at 40° C. in vacuo for 19 hours to give 55.4 kg diethyl (3-chloro-4-fluorophenyl)aminomethylenepropanedioate, m.p. 71.5°-72.5° C. (85% yield). The combined filtrate and washes were concentrated to 54 L and a second crop was isolated and dried as before to give 5.6 kg additional product, m.p. 71.5°-72.5° C. for a combined yield of 93.5%.

Workup

  1. customwas obtained
  2. additionwas added to a 100 gallon glass-lined unit
  3. temperatureto reflux for one hour
  4. temperaturecooled
  5. customto near 0° C.
  6. stirringwith stirring
  7. customCrystallization
  8. customhad reached 27° C. during the cooling process
  9. stirringStirring
  10. waitwas continued for another hour
  11. filtrationthe solid product was filtered on a ceramic filter
  12. washthe filter cake was washed with 3×16 L cold (1°-5° C.) ethanol
  13. customThe product was dried at 40° C. in vacuo for 19 hours

Sources & evidence

ORD record
ord-91d94e07d1d94229bfd48964bdd3a4bb
Source dataset
uspto-grants-1989_09
Patent number
US04868305

Reaction notes

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