Hydrochloric Acid → 4-[N-Benzyl-3-(4-chlorobenzyl)-piperidin-3-yl]-2,4-dioxobutanoic acid Hydrochloride

HRID 53237Notes

Reaction equation

HRID 53237 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:22](=[O:24])[CH3:23])([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](OC)(=[O:30])[C:26]([O:28]C)=[O:27].[H-].[Na+].C(=O)(O)[O-].[Na+].Cl>C(COC)OC.O1CCCC1>[ClH:21].[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:22](=[O:24])[CH2:23][C:25](=[O:30])[C:26]([OH:28])=[O:27])([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11120Dimethyl oxalateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 19962175N-Benzyl-3-acetyl-3-(4-chlorobenzyl)-piperidine

Product 1

HCID 677146154-[N-Benzyl-3-(4-chlorobenzyl)-piperidin-3-yl]-2,4-dioxobutanoic acid HydrochlorideYield 10.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of N-Benzyl-3-acetyl-3-(4-chlorobenzyl)-piperidine (492 mg, 1.44 mmol) and dimethyl oxalate (201 mg, 1.7 mmol) in dimethoxyethane (20 mL) was treated with sodium hydride (140 mg of a 60% dispersion in mineral oil, 3.4 mmol) and heated to reflux for 5 hours. The reaction was then cooled to room temperature, poured into saturated sodium bicarbonate (100 mL) and extracted with ethyl acetate (3×100 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The crude ester thus obtained was purified by chromato-graphy on silica gel eluting with 10% methanol/chloroform. The material thus obtained was dissolved in tetrahydrofuran (5 mL) and 3N HCl (20 mL) and heated to reflux for 1 hour. The reaction was then cooled to room temperature, and concentrated at reduced pressure. The residue was triturated with tetrahydrofuran and the solid collected by filtration and crystallized from isopropanol to give 35 mg of the title compound. mp. 160°-165° C.

Workup

  1. temperatureheated
  2. temperatureto reflux for 5 hours
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customThe crude ester thus obtained
  8. customwas purified by chromato-graphy on silica gel eluting with 10% methanol/chloroform
  9. customThe material thus obtained
  10. temperatureto reflux for 1 hour
  11. temperatureThe reaction was then cooled to room temperature
  12. concentrationconcentrated at reduced pressure
  13. customThe residue was triturated with tetrahydrofuran
  14. filtrationthe solid collected by filtration
  15. customcrystallized from isopropanol

Sources & evidence

ORD record
ord-99859e59df4e4d4a891b01fc663e59ef
Source dataset
uspto-grants-1997_04
Patent number
US05618830

Reaction notes

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