Oxalic Acid → 4-[Bis(4-fluorophenyl)hydroxymethyl]-1-piperidinebutanamide ethanedioate

HRID 345492Notes

Reaction equation

HRID 345492 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.Cl[CH2:24][CH2:25][CH2:26][C:27]([NH2:29])=[O:28].C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40]>CN(C)C=O.O>[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([OH:9])[CH:10]2[CH2:11][CH2:12][N:13]([CH2:24][CH2:25][CH2:26][C:27]([NH2:29])=[O:28])[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 971Oxalic AcidHCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 755644-ChlorobutyramideHCID 11208889Bis(4-fluorophenyl)(piperidin-4-yl)methanol

Product 1

HCID 867451674-[Bis(4-fluorophenyl)hydroxymethyl]-1-piperidinebutanamide ethanedioateYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.9 g (0.040 mole) of 4-chlorobutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 24 h. The mixture was poured into 1.5 L of water and extracted twice with 500 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column eluted with methanol-methylene chloride (1:2). The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. The glass was converted to the oxalic acid salt, and the solid was recrystallized from ethyl acetate/2-propanol to yield 0.7 g (9%) of the title compound as a white solid containing 0.25 mole H2O, mp 177°-179° C.

Workup

  1. extractionextracted twice with 500 mL portions of ethyl acetate
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customto give a dark oil
  6. customThe oil was purified by column chromatography
  7. washeluted with methanol-methylene chloride (1:2)
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was partitioned between methylene chloride and water
  11. washThe methylene chloride layer was washed with water and brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated under reduced pressure
  14. customto give a glass
  15. customthe solid was recrystallized from ethyl acetate/2-propanol

Sources & evidence

ORD record
ord-aec586dfebeb4ff5ac6ea0f33730b9ad
Source dataset
uspto-grants-1991_10
Patent number
US05057524

Reaction notes

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