Potassium Carbonate → HCID 21473404, compound

HRID 2294107Notes

Reaction equation

HRID 2294107 reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6].Cl.[Cl:13][CH2:14][CH2:15][NH:16][CH2:17][CH2:18]Cl.C(=O)([O-])[O-].[K+].[K+]>C(O)CCC>[ClH:13].[F:1][CH:2]([F:11])[O:3][C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[N:6]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 9346202-(Difluoromethoxy)aniline

Product 1

HCID 21473404HCID 21473404, compoundYield 13.6%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-difluoromethoxyaniline (5.14 g, 32.3 mmol) and bis(chloroethyl)amine hydrochloride (5.8 g, 32.5 mmol) in 50 mL of n-butanol was heated at reflux for 48 hours. Potassium carbonate (8.9 g, 64.5 mmol) was added and heated at reflux for approximately 24 hours. The mixture was extracted with 2N hydrochloric acid and the extract cooled to approximately 0° C. and then basified with sodium hydroxide to give a precipitate. The precipitate was extracted with ethyl acetate. The ethyl acetate extract was washed with brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography eluting with 5% methanol/methylene chloride. Product fractions were combined and concentrated. The residue was crystallized from hydrochloric acid in methanol to give 1-[2-(difluoromethoxy)phenyl]piperazine hydrochloride (1.32 g, 4.38 mmol), m.p. 165°-176° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 48 hours
  3. temperatureheated
  4. temperatureat reflux for approximately 24 hours
  5. extractionThe mixture was extracted with 2N hydrochloric acid
  6. customto give a precipitate
  7. extractionThe precipitate was extracted with ethyl acetate
  8. extractionThe ethyl acetate extract
  9. washwas washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography
  13. washeluting with 5% methanol/methylene chloride
  14. concentrationconcentrated
  15. customThe residue was crystallized from hydrochloric acid in methanol

Sources & evidence

ORD record
ord-9c3daae4c36a4be0a63dc32d09e9d8f8
Source dataset
uspto-grants-1997_11
Patent number
US05688795

Reaction notes

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