Formaldehyde → Methyl 11-[2-(4-methylpiperazino)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate

HRID 359002Notes

Reaction equation

HRID 359002 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C=O.F[C:11](F)(F)C(O)=O.[CH2:17]=[C:18]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH2:22][O:21][C:20]2[CH:29]=[CH:30][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:32][C:19]1=2>ClCC(Cl)(Cl)Cl>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:11][CH:17]=[C:18]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[CH2:22][O:21][C:20]3[CH:29]=[CH:30][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:32][C:19]2=3)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 531671-MethylpiperazineHCID 10106958HCID 10106958, compound

Product 1

HCID 53817464Methyl 11-[2-(4-methylpiperazino)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate

Reagents, catalysts & solvents 1

HCID 124181,1,1,2-TetrachloroethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

1-Methylpiperazine, 30 ml, and 74 g of paraformaldehyde were dissolved in 2 l of tetrachloroethane and 100 ml of trifluoroacetic acid was dropwise added to the solution. After stirring at 60° C. for 2 hours, a solution of 36 g of methyl 11-methylene-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate in 600 ml of tetrachloroethane was dropwise added to the reaction mixture followed by stirring at 90° C. for further 3 hours. The reaction mixture was concentrated to dryness under reduced pressure and 4N hydrochloric acid aqueous solution was added to the residue to adjust pH to 1. Then, the mixture was washed with diethyl ether. Thereafter, 10N sodium hydroxide aqueous solution was added to adjust pH to 13. Extraction was performed with 3 l of methylene chloride. After washing with saturated sodium chloride aqueous solution and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluting solvent; hexane:ethyl acetate:triethylamine=5:5:1) to give 44 g of colorless oily methyl 11-[2-(4-methyl-1-piperazinyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate.

Workup

  1. stirringby stirring at 90° C. for further 3 hours
  2. concentrationThe reaction mixture was concentrated to dryness under reduced pressure and 4N hydrochloric acid aqueous solution
  3. additionwas added to the residue
  4. washThen, the mixture was washed with diethyl ether
  5. additionThereafter, 10N sodium hydroxide aqueous solution was added
  6. extractionExtraction
  7. washAfter washing with saturated sodium chloride aqueous solution
  8. dry with materialdrying over anhydrous sodium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. washThe resulting residue was subjected to silica gel column chromatography (eluting solvent; hexane:ethyl acetate:triethylamine=5:5:1)

Sources & evidence

ORD record
ord-d357b06069834f3e9d709ef4f44754cc
Source dataset
uspto-grants-1991_03
Patent number
US04999363

Reaction notes

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