Formaldehyde → Ethyl 1-(4-fluorophenyl)-4-hydroxy-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate

HRID 1065258Notes

Reaction equation

HRID 1065258 reaction equation
[CH2:1]=O.[C:3]([C:6]1([NH:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]1)(=[O:5])[NH2:4]>CN(C)C=O>[F:24][C:21]1[CH:20]=[CH:19][C:18]([N:17]2[C:6]3([CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]3)[C:3](=[O:5])[NH:4][CH2:1]2)=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 30189781-(Ethoxycarbonyl)-4-(4-fluoroanilino)piperidine-4-carboximidic acid

Product 1

HCID 12834315Ethyl 1-(4-fluorophenyl)-4-hydroxy-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6.9 parts of paraformaldehyde in 100 parts of N,N-dimethylformamide are added portionwise 46.3 parts of ethyl 4-carbamoyl-4-(4-fluorophenylamino)-1-piperidinecarboxylate. The whole is stirred and refluxed for 20 hours. Then 50 parts of the solvent are distilled off (t°: 142°-152° C.). A second portion of 1 part of paraformaldehyde in 50 parts of N,N-dimethylformamide is added and stirring and refluxing is continued for 48 hours. The N,N-dimethylformamide is distilled off to a volume of about 50 parts and the distillate is poured onto water. The water is decanted and the residue is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated. The residue is triturated in 2,2'-oxybispropane. The product is filtered off and crystallized from a mixture of benzene and 2,2'-oxybispropane, yielding 17.5 parts of ethyl 1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]decane-8-carboxylate; mp. 153° C.

Workup

  1. temperaturerefluxed for 20 hours
  2. distillationThen 50 parts of the solvent are distilled off (t°: 142°-152° C.)
  3. additionA second portion of 1 part of paraformaldehyde in 50 parts of N,N-dimethylformamide is added
  4. stirringstirring
  5. temperaturerefluxing
  6. distillationThe N,N-dimethylformamide is distilled off to a volume of about 50 parts
  7. additionthe distillate is poured onto water
  8. customThe water is decanted
  9. extractionthe residue is extracted with trichloromethane
  10. washThe extract is washed with water
  11. customdried
  12. filtrationfiltered
  13. customevaporated
  14. customThe residue is triturated in 2,2'-oxybispropane
  15. filtrationThe product is filtered off
  16. customcrystallized from a mixture of benzene and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-51fc458bfebb41599fccc3512d77bed0
Source dataset
uspto-grants-1982_05
Patent number
US04329353

Reaction notes

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